Early Intervention and Cumulative Life Course Impairment in psoriasis: a Review.

Psoriasis is a chronic, systemic, inflammatory disease affecting the skin, joints, and other organs. Psoriasis negatively affects patients' quality of life, causing social anxiety and negative coping, thus determining a cumulative life course impairment (CLCI). The concept of CLCI in psoriasis is reinforced by the understanding that psoriasis-associated comorbidities and stigma accumulate over a patient's life course, resulting from an interaction between the burden of stigmatization, physical and psychological co-morbidities, coping strategies, and external factors. The concept may help identify more vulnerable patients and facilitate more appropriate treatment decisions or earlier referrals. Although some potential risk factors for CLCI have been clarified, no all-encompassing screening tools are available. Patients at risk for CLCI should be identified by applying clinical, personal and psychosocial indicators and predictors individually. Early intervention in psoriasis treatment could improve long-term patient outcomes and modify the disease course. However, more research is needed to define what constitutes "early" intervention clearly and to identify the most effective strategies for implementation. From a preventive point of view, it is helpful to identify early interventions aimed at reducing the risk of CLCI and establishing a new life course trajectory in patients with psoriasis. This review summarizes the state of the art on CLCI and psoriasis, highlighting knowledge gaps and future directions to make CLCI control a possible goal for therapies.

Short-, mid- and long-term efficacy of dupilumab in moderate to severe atopic dermatitis: a real life multicenter Italian study on 2576 patients.

BACKGROUND: The efficacy and safety of dupilumab in atopic dermatitis (AD) have been defined in clinical trials but limited real-world evidence on long term treatment outcomes are currently available to inform clinical decisions. OBJECTIVES: to describe long-term effectiveness and safety of dupilumab up to 48 months in patients with moderate-to-severe AD. METHODS: a multicenter, retrospective, dynamic cohort study was conducted to assess long term effectiveness and safety of dupilumab in patients with moderate to severe AD in a real-world setting. Predictors of minimal disease activity (MDA) optimal treatment target criteria (defined as the simultaneous achievement of EASI90, itch NRS score ≤1, sleep NRS score ≤1 and DLQI ≤1) were investigated. RESULTS: 2576 patients were enrolled from June 2018 to July 2022. MDA optimal treatment target criteria were achieved by 506 (21.91%), 769 (40.63%), 628 (50.36%), 330 (55.37%) and 58 (54.72%) of those that reached 4, 12, 24, 36 and 48 months of follow-up, respectively. Logistic regression revealed a negative effect on MDA achievement for conjunctivitis and food allergy at all timepoints. Adverse events (AE) were mild and were observed in 373 (15.78%), 166 (7.02%), 83 (6.43%), 27 (4.50%) and 5 (4.55%) of those that reached 4, 12, 24, 36 and 48 months of follow-up. Conjunctivitis was the most frequently reported AE during the available follow-up. AE led to treatment discontinuation in <1% of patients during the evaluated time periods. CONCLUSION: High long-term effectiveness and safety of dupilumab were confirmed in this dynamic cohort of patients with moderate to severe AD, regardless of clinical phenotype and course at baseline. Further research will be needed to investigate the effect of Th2 comorbidities and disease duration on the response to dupilumab and other newer therapeutics for AD.

Association between maternal dupilumab exposure and pregnancy outcomes in patients with moderate-to-severe atopic dermatitis: A nationwide retrospective cohort study.

BACKGROUND: There is limited epidemiological evidence on outcomes associated with dupilumab exposure during pregnancy; monitoring pregnancy outcomes in large populations is required. OBJECTIVE: To investigate the potential association between exposure to dupilumab in pregnant women with atopic dermatitis and any adverse pregnancy, neonatal, congenital and post-partum outcomes. METHODS: We performed a multicentre retrospective cohort study across 19 Italian tertiary referral hospital. Childbearing women were eligible if aged 18-49 years and carried out the pregnancy between 1 October 2018 and 1 September 2022. RESULTS: We retrospectively screened records of 5062 patients receiving dupilumab regardless of age and gender, identifying 951 female atopic dermatitis patients of childbearing age, 29 of whom had been exposed to the drug during pregnancy (3%). The median duration of dupilumab treatment prior to conception was 22.5 weeks (range: 3-118). The median time of exposure to the drug during pregnancy was 6 weeks (range: 2-24). All the documented pregnancies were unplanned, and the drug was discontinued in all cases once pregnancy status was reported. The comparison of the study cohort and the control group found no significant drug-associated risk for adverse pregnancy, congenital, neonatal or post-partum outcomes. The absence of a statistically significant effect of exposure on the event was confirmed by bivariate analysis and multivariate analysis adjusted for other confounding factors. CONCLUSIONS: This cohort of pregnant patients exposed to dupilumab adds to the existing evidence concerning the safety of biologic agents in pregnancy. No safety issues were identified regarding the primary outcome assessed. In clinical practice, these data provide reassurance in case of dupilumab exposure during the first trimester. However, the continuous use of dupilumab throughout pregnancy warrants further research.

Clinical and Ultrasound Efficacy of Topical Hypertonic Cream (Jovita Osmocell®) in the Treatment of Cellulite: A Prospective, Monocentric, Double-Blind, Placebo-Controlled Study.

Background and Objectives: Cellulite, or edemato-fibro-sclerotic panniculopathy (EFP), is characterized by dermal and hypodermal changes leading to adipose tissue accumulation and compromised venous circulation. This study investigates the efficacy of a hypertonic cream containing concentrated sodium chloride (Jovita Osmocell®) in addressing water retention and structural alterations in adipose tissue, aiming to interrupt the cellulite formation process. Materials and Methods: A 12-week, prospective, monocentric, double-blind, placebo-controlled study enrolled 30 female subjects with grade II or III cellulite. Patients were randomized to receive hypertonic cream or a placebo. Thigh circumference, ultrasound evaluations, and standardized photographs were collected at baseline, intermediate, and endpoint visits. Adverse events were monitored. Results: After 84 days, the hypertonic cream group exhibited a significant reduction in thigh circumference compared to the placebo group (p = 0.0037). B-mode ultrasound examinations revealed significant changes in the parameters studied, such as the thickness of the subcutaneous tissue. No statistically significant changes were noticed in the placebo group. Volunteers reported the investigational product's pleasantness and good anti-cellulite activity, with no reported adverse events. Conclusions: The hypertonic cream demonstrated efficacy in reducing thigh circumference, addressing water retention and structural alterations in adipose tissue. The proposed mechanism involves osmosis, releasing accumulated fluids between fat cells, supporting drainage, and reducing inflammation. This study supports the efficacy and safety of hypertonic sodium chloride emulsions in cellulite treatment and confirms safety and user satisfaction.

Thin Amelanotic and Hypomelanotic Melanoma: Clinicopathological and Dermoscopic Features.

Background and Objectives: Amelanotic/hypomelanotic melanomas (AHMs) account for 2-8% of all cutaneous melanomas. Due to their clinical appearance and the lack of specific dermoscopic indicators, AHMs are challenging to diagnose, particularly in thinner cutaneous lesions. The aim of our study was to evaluate the clinicopathological and dermoscopic features of thin AHMs. Identifying the baseline clinical-pathological features and dermoscopic aspects of thin AHMs is crucial to better understand this entity. Materials and Methods: We divided the AHM cohort into two groups based on Breslow thickness: thin (≤1.00 mm) and thick (>1.00 mm). This stratification helped identify any significant clinicopathological differences between the groups. For dermoscopic analysis, we employed the "pattern analysis" approach, which involves a simultaneous and subjective assessment of different criteria. Results: Out of the 2.800 melanomas analyzed for Breslow thickness, 153 were identified as AHMs. Among these, 65 patients presented with thin AHMs and 88 with thick AHMs. Red hair color and phototype II were more prevalent in patients with thin AHMs. The trunk was the most common anatomic site for thin AHMs. Patients with thin AHMs showed a higher number of multiple melanomas. Dermoscopic analysis revealed no significant difference between thin AHMs and thick AHMs, except for a more frequent occurrence of residual reticulum in thin AHMs. Conclusions: Thin AHMs typically affect individuals with lower phototypes and red hair color. These aspects can be related to the higher presence of pheomelanin, which provides limited protection against sun damage. This also correlates with the fact that the trunk, a site commonly exposed to intermittent sun exposure, is the primary anatomical location for thin AHMs. Multiple primary melanomas are more common in patients with thin AHMs, likely due to an intrinsic predisposition as well as greater periodic dermatologic follow-ups in this class of patients. Apart from the presence of residual reticulum, no other significant dermoscopic differences were observed, complicating the differential diagnosis between thin and thick AHMs based on dermoscopy alone.

Adult-Onset Linear Morphea (en coupe de sabre) of the Face Successfully Treated with Photoactivated Low-Temperature Platelet-Rich Plasma: A Valid Therapeutic Option.

Localized scleroderma (also known as morphea) is a chronic autoimmune disorder characterized by depressed, fibrotic, and dyschromic cutaneous lesions. It has a significant impact on the patient's daily life due to the unaesthetic evolution of the cutaneous lesions. Morphea is clinically divided into linear, circumscribed (plaque), generalized, pansclerotic, and mixed forms. Linear morphea en coupe de sabre (LM) usually arises in childhood. However, in about 32% of cases, it may arise in adulthood, showing a more aggressive course with also an increased risk of systemic involvement. Methotrexate is the first-line treatment for LM, although systemic steroids, topical agents (corticosteroids and calcineurin inhibitors), hyaluronic acid injections, and hydroxychloroquine or mycophenolate mofetil are valid therapeutic options. In any case, these treatments are not always effective and sometimes can be associated with important side effects and/or not tolerated by the patients. In this spectrum, platelet-rich plasma (PRP) injection can be considered a valid and safe alternative since PRP injections in the skin induce the release of anti-inflammatory cytokines and growth factors, thus reducing inflammation and increasing collagen remodeling. Herein, we describe a successful treatment of an adult-onset LM en coupe de sabre with photoactivated low-temperature PRP (Meta Cell Technology Plasma) sessions, showing an important local improvement of the lesion and patient satisfaction.

New onset atopic dermatitis and psoriasis in the same patients under biologic treatments: The role of systemic treatments as a possible trigger.

Atopic dermatitis (AD) and psoriasis (PsO) are among the most common diseases in the daily clinical practice. Usually, AD and PsO are reported as two diseases that cannot coexist in the same patient because this requires the activation of opposing inflammatory pathways. Anyway, some reports highlight how AD and PsO may coexist in the same patient or develop consequently. In this short report we collected 12 patients that developed new AD or PsO. Among them, eight patients (n = 8; 3M:5F) with a previous diagnosis of PsO, developed subsequently an AD with a mean time of onset of 71.5 months. Out of eight patients, four patients where in treatment with ustekinumab, one with ixekizumab, two with adalimumab, and one with guselkumab. All new onset AD have been treated with topical medicaments, except one case that performed dupilumab. Contrariwise, four patients with a baseline AD developed a PsO with a mean time of onset of 25 months. Two AD patients were under dupilumab treatment, while the other two patients performed only topical treatments. All patients showed an improvement of the new onset PsO with topical treatment only. This report highlights how AD and PsO are not mutually exclusive diseases. The mechanisms by which AD patients develop PsO or psoriatic patients develop AD are still not very clear; some triggers can promote these processes, such as systemic therapies. Therefore, clinicians should carefully evaluate any changes in these patients, in order to reach a correct diagnosis and carry out a relative treatment.

Syphilis: a mini review of the history, epidemiology and focus on microbiota.

Syphilis is a chronic systemic infectious disease caused by the spirochaete bacterium Treponema pallidum(syphilis treponeme). In recent decades there has been a drastic increase in cases of syphilis,with a relative increase in scientific interest in this regard. However, the data concerning the studyof microbiota in syphilis are few and very scattered.This brief review provides a quick update on the disease, with particular attention to the role of themicrobiota, an aspect not always adequately considered in the evaluation of the pathology. The usualcoexistence of different sexually transmitted diseases in the same patients led us to delve also intothe possible role of the microbiota in the pathogenesis of syphilis; indeed, not all sexual contactslead to infections, suggesting that host immunity and local microbiota could modulate the historyof sexually transmitted disease. In both males and females, alteration of the microbiota may be involvedin syphilis as well as in the other sexually transmitted diseases. Finally, since 9% of the totalproteome of T. pallidum is spent for transportome, the latter may provide essential nutrients, makingT. pallidum able to adapt to a diverse range of microenvironments and stresses in the human host.

Case Report of Dermoscopic Aspects and Reflectance Confocal Microscopy Description of Segmental Leiomyoma and Relative Management.

Cutaneous leiomyoma is a benign tumor, mainly composed of smooth muscle cells and arising from the arrector pili muscle of hair follicles. The diagnosis of leiomyomas is of paramount importance, as they can often be associated with underlying malignancies (e.g., renal cell carcinoma, leiomyosarcoma) and specific genetic mutations. We report the case of a 27-year-old Caucasian male patient that presented to our attention with a rare segmental and Zoosteriform type II leiomyoma. We performed an analysis of the cutaneous lesions using dermoscopy, reflectance confocal microscopy (RCM) and histology. We found that, using dermoscopy, the leiomyomas showed a dermatofibroma-like appearance with a central hypopigmented area, peripheral delicate hyperpigmentation and also erythematous areas and ectatic vessels. RCM, although not specific, showed groups of hypo-reflective areas distributed in the most superficial papillary dermis, which in histology and immunohistochemistry corresponded to the most superficial protrusions in the papillary dermis of the tumoral bundles. Finally, we discuss the management of patients with multiple leiomyomas and stress the fact that, in the cases of multiple leiomyomas, an annual sonography of the kidneys associated with dermatological and (in women) gynecological consultations are needed to ensure the early identification of an underlying tumor. A genetic consultation to detect an eventual FH mutation is recommended, but since in some cases the FH result may be negative, the above recommended controls remain always of paramount importance.

Investigating the Safety and Efficacy of Platelet-Rich Plasma (PRP) Treatment for Female Androgenetic Alopecia: Review of the Literature.

Background: female androgenetic alopecia (FAGA) is a common cause of non-scarring alopecia in women, affecting approximately 40% of women by age 50, bearing a significant psychosocial burden on affected patients. Platelet-rich plasma (PRP) has been widely investigated as a potential effective treatment for several dermatological conditions, including male androgenetic alopecia (MAGA). However, few studies have been conducted focusing on the use of PRP in FAGA. The aim of this review was to identify reports that investigated the use of PRP for the treatment of FAGA. Methods: Electronic databases of MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) from inception to September 2020 have been searched using different combinations of the following terms: "androgenetic alopecia," "FAGA," "female pattern hair loss," "platelet-rich fibrin," "platelet-rich plasma," and "PRP". Results and conclusions: Eight (n = 8) clinical studies consistent with our research were identified. A total of 197 subjects has been enrolled in the included studies. All of them were adult female patients (mean age: 38.9) affected by female pattern hair loss. PRP is a well-tolerated procedure which showed promising results in males-only and mixed populations of AGA patients. PRP showed to produce high levels of satisfaction and improvement in the quality of life in patients affected by FAGA. In the light of this evidence, PRP may be proposed in patients who did not respond or did not tolerate topical minoxidil, as well as in combination with topical and oral treatments.

Pilot Study on the Use of the "Monocyte-Rich" Platelet-Rich Plasma in Combination with 1927 nm Fractional and 308 nm Excimer Lasers for the Treatment of Vitiligo.

Background and objectives: Vitiligo is an acquired chronic and idiopathic skin disorder, characterized by selective loss of melanocytes and resulting in a cutaneous depigmentation. Treatment for vitiligo remains a challenge for dermatologists; thus, it is frustrating both for physicians and patients. The objective of this study was to evaluate a combination treatment characterized by the use of a leukocyte-rich platelet-rich plasma, which is particularly rich in monocytes (defined here as monocyte-rich PRP), in combination with a 1927 nm fraxel laser and a 308 nm excimer laser. Materials and Methods: Treatment with monocyte-rich PRP combined with 1927 nm fraxel laser and 308 nm excimer laser was performed in nine sessions in 80 days and the median follow-up of the patients was 10 months. A total of 27 Caucasian patients were included in the present study. The median age of patients was 41 years, ranging between 20 and 69 years. Results: A re-pigmentation occurred in 16 cases (59%) with a reduction of the Vitiligo Extent Score (VES) and absence of re-pigmentation in untreated areas. Performing a rank correlation between VES and re-pigmentation in the treated areas, we found that there was a significant correlation (p < 0.0001). The presence of progressive vitiligo (p = 0.1) and the anatomic areas (p = 0.1) did not influence the treatment. Untreated areas did not show any improvement of the depigmented lesions, except in one case (p < 0.0001). Conclusions: in this report, we show for the first time how PRP rich in monocytes, in combination with laser therapies, gives a long therapeutic response, which persists even after 10 months of follow-up.

Systemic immunobiological, immunosuppressant, and oncologic agents for the treatment of dermatologic diseases during the SARS-CoV-2 (COVID-19) pandemic emergency: A quick review for a quick consultation.

The precision medicine era has helped to better manage patients with immunological and oncological diseases, improving the quality of life of this class of patients. Regarding the management of these patients and positivity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), currently, limited data are available and information is evolving. In this quick review, we have analyzed the mechanisms of action and related infective risk of drugs used for the treatment of immune-mediated and oncologic skin conditions during the daily clinical practice. In general, immunosuppressant and antineoplastic agents for dermatologic treatments do not require suspension and do not require special measures, if not those commonly observed. In the case of a coronavirus disease (COVID-19) patient with complications (such as pneumonia, respiratory failure), treatment suspension should always be considered after taking into account the general condition of the patient, the risk-benefit ratio, and the pathophysiology of COVID-19 infection. The COVID-19 emergency pandemic does not imply undertreatment of existing skin conditions, which together with the SARS-CoV-2 infection may jeopardize the patient's life.

Lentigo maligna of the face: A quantitative simple method to identify individual patient risk probability on dermoscopy.

BACKGROUND/OBJECTIVES: The clinical and dermoscopic differential diagnosis of flat pigmented facial lesions represents a great challenge for the clinicians. Our aim was to report a quantitative method based on dermoscopic features to better classify pigmented facial lesions. METHODS: This is a retrospective case-series study that analysed the dermoscopic features of 582 pigmented facial lesions. RESULTS: The individual patient probability of lentigo maligna (LM) was predicted by a multivariate model, with an accuracy of 0.72. According to the odds ratio at the multivariate analysis, an individual scoring index was assigned to each criterion, and a value of 4.56 was identified as optimal cut-off point. Up to a score of 2.5, the probability that a lesion is an LM is 0. The probability increases from 10 to 50% for a score ranging between 4.5 and 6. It is about 90% for a score of 7. CONCLUSION: The optimal cut-off point obtained and the curve that identifies the probability of a patient having a LM could improve the classification and the management strategies of equivocal pigmented facial lesions.

Paraneoplastic Pemphigus: Insight into the Autoimmune Pathogenesis, Clinical Features and Therapy.

Paraneoplastic pemphigus is a rare autoimmune skin disease that is always associated with a neoplasm. Usually, oral, skin, and mucosal lesions are the earliest manifestations shown by paraneoplastic pemphigus patients. The pathogenesis of paraneoplastic pemphigus is not yet completely understood, although some immunological aspects have been recently clarified. Because of its rarity, several diagnostic criteria have been proposed. Besides, several diagnostic procedures have been used for the diagnosis, including indirect immunofluorescence, direct immunofluorescence, and ELISA. We reviewed the most recent literature, searching on PubMed "paraneoplastic pemphigus". We included also papers in French, German, and Spanish. We found 613 papers for "paraneoplastic pemphigus". Among them, 169 were review papers. Because of its varying clinical features, paraneoplastic pemphigus still represents a challenge for clinicians. Furthermore, diagnosis and management of paraneoplastic pemphigus requires close collaboration between physicians, including dermatologist, oncologist, and otorhinolaryngologist.

Unmet diagnostic needs in contact oral mucosal allergies.

The oral mucosa including the lips is constantly exposed to several noxious stimuli, irritants and allergens. However, oral contact pathologies are not frequently seen because of the relative resistance of the oral mucosa to irritant agents and allergens due to anatomical and physiological factors. The spectrum of signs and symptoms of oral contact allergies (OCA) is broad and a large number of condition can be the clinical expression of OCA such as allergic contact stomatitis, allergic contact cheilitis, geographic tongue, oral lichenoid reactions, burning mouth syndrome. The main etiological factors causing OCA are dental materials, food and oral hygiene products, as they contain flavouring agents and preservatives. The personal medical history of the patient is helpful to perform a diagnosis, as a positive history for recent dental procedures. Sometimes histology is mandatory. When it cannot identify a direct cause of a substance, in both acute and chronic OCA, patch tests can play a pivotal role in the diagnosis. However, patch tests might have several pitfalls. Indeed, the presence of metal ions as haptens and specifically the differences in their concentrations in oral mucosa and in standard preparation for patch testing and in the differences in pH of the medium might result in either false positive/negative reactions or non-specific irritative reactions. Another limitation of patch test results is the difficulty to assess the clinical relevance of haptens contained in dental materials and only the removal of dental materials or the avoidance of other contactant and consequent improvement of the disease may demonstrate the haptens' responsibility. In conclusion, the wide spectrum of clinical presentations, the broad range of materials and allergens which can cause it, the difficult interpretation of patch-test results, the clinical relevance assessment of haptens found positive at patch test are the main factors that make sometimes difficult the diagnosis and the management of OCA that requires an interdisciplinary approach to the patient.

Early Angiosarcoma of the Scalp: A Clinicopathological Pitfall.

Angiosarcoma (AS) is a rare malignant vascular tumor, which affects mainly elderly patients. After the diagnosis, the mean overall survival of patients is 30 months. The variable presentation of the malignancy, the benign appearance of the cutaneous lesions, and the minimal histological changes in early lesions can sometimes delay the correct diagnosis. The authors report a case of an 80-year-old white male patient, with a painless and ecchymotic lesion of the scalp, which histologically showed minimal pathological atypia, conclusive for a diagnosis of AS with minimal histological changes. The authors discuss the main and most emblematic cases of AS initially misdiagnosed for other cutaneous diseases reported in the literature, noting that in some cases, also the histology can be treacherous and a trap for the dermatopathologist. The recent findings on MYC, FLT4 and KDR amplification, and the relative therapeutic perspectives are also discussed. Finally, the authors draw up some pathological cornerstones, which could improve the diagnosis, above all in early lesions with minimal atypia.