Topical beta-blockers in dermatologic therapy.

An increasing use of beta-blockers in dermatology has been described over the last 10 years, despite the fact that their use in diseases other than infantile hemangiomas is off-label. This review discusses the emerging role of topical beta-blockers in the treatment of infantile hemangioma, but also pyogenic granuloma, Kaposi sarcoma, wounds and nail paronychia. Data in literature demonstrate that topical beta-blockers are a safe and valid therapeutic option in numerous cutaneous diseases. Side effects are mainly restricted to the application site. Further studies and randomized trials may contribute to reinforce the role of topical beta-blockers in the dermatological armamentarium.

Management of melanoma patients during COVID-19 pandemic in an Italian skin unit.

Due to the COVID-19 crisis, many scheduled medical and surgical activities have been suspended. This interruption to the healthcare system can negatively affect the diagnosis and management of melanoma. Neglecting melanoma throughout the outbreak may be associated with increased rates of mortality, morbidity, and healthcare expenses. We performed a retrospective review of all dermatological and surgical activity performed in our Melanoma Skin Unit between 23 February 2020 and 21 May 2020 and compared these data with those from the same period in 2019. During the lockdown period, we observed a decrease in dermatologic follow-up (DFU) (-30.2%) and in surgical follow-up (SFU) (-37%), and no modification of melanoma diagnosis (-3%). Finally, surgical excisions (SE) (+ 31.7%) increased, but sentinel lymph node biopsy (SLNB) (-29%) and lymph node dissections(LND) (-64%) decreased compared to the same period in 2019. Our experience supports the continuation of surgical and diagnostic procedures in patients with melanoma during the COVID-19 pandemic. Surgical and follow-up procedures for the diagnosis and treatment of melanoma should not be postponed considering that the pandemic is lasting for an extended period.

The Burden of Autosomal Recessive Congenital Ichthyoses on Patients and their Families: An Italian Multicentre Study.

Autosomal recessive congenital ichthyoses (ARCI) are characterized by generalized skin scaling, hyperkeratosis, erythroderma, and disabling features affecting the skin (palmoplantar keratoderma, fissures, pain, itch), eyes, ears, and joints. Disease severity and chronicity, patient disfigurement, and time and costs required for care impose a major burden on quality of life. This multicentre cross-sectional study investigated the impact of ARCI on quality of life of patients and families, using the Dermatology Life Quality Index (DLQI), the Children DLQI (CDLQI) and Family Burden of Ichthyosis (FBI) questionnaires. Disease severity was assessed by a dermatologist. A total of 94 patients were recruited, of whom 52 (55.3%) children. Mean age was 20.1 (median 13.5) years. The mean CDLQI/DLQI score was 7.8, and 21 patients scored >10, indicating a major impairment in quality of life: symptoms, feelings and treatment problems were the most affected domains of quality of life. FBI showed a major repercussion on psychological factors and work. The results of this study highlight the impact of ARCI on specific aspects of patient and family life, underlining the need for psychological support.

Extracellular fraction of adipose tissue as an innovative regenerative approach for vitiligo treatment.

Vitiligo is a common, disfiguring autoimmune disease that negatively affects patients' self-esteem and quality of life. Current treatments are moderately effective in reversing disease and promoting melanocyte regeneration. Thus, therapeutic advanced strategies are emerging from regenerative medicine. It has recently emerged that adipose tissue secretome may be used as a cell-free therapy in skin regeneration since paracrine functions of adipose-derived stem cells alone are responsible for most of the therapeutic effect of stem cells in several animal disease models. In this study, we tested the effect of adipose tissue extracellular fraction (AT-Ex) isolated from lipoaspirates on dermal and epidermal vitiligo cells in vitro. Using this experimental model, we demonstrated that molecules secreted by adipose tissue ameliorate the capability to counteract oxidative stress by a physiological stimulation of intracellular antioxidant enzymes and positively impact on cell proliferation. Due to the presence of Wnt-secreted factors, AT-Ex treatment promotes glycogen synthase kinase 3ß inactivation and consequently Wnt/ß-catenin pathway activation. Collectively, our findings show that AT-Ex could be useful as a natural approach to improve treatment of vitiligo.

Involvement of non-melanocytic skin cells in vitiligo.

Despite melanocytes are the key players in vitiligo, a continuous cross-talk between epidermal and dermal cells may strictly affect their functionality, in both lesional skin and non-lesional skin. Focusing on this interplay, we have reviewed existing literature supporting evidence on cellular and functional alterations of surrounding epidermal keratinocytes, extracellular matrix (ECM) proteins and fibroblasts in the underlying dermal compartment that may contribute to melanocyte disappearance in vitiligo. We have also examined some clinical and therapeutic aspects of the disease to sustain the non-exclusive involvement of melanocytes within vitiligo. As a result, a different and more complex scenario has appeared that may enable to provide better understanding about origins and progress of vitiligo and that should be considered in the evaluation of new treatment approaches.

Adalimumab in severe plaque psoriasis of childhood: A multi-center, retrospective real-life study up to 52 weeks observation.

The objective of this study is to determine drug effectiveness and safety of the tumor necrosis factor-alpha blocker monoclonal antibody adalimumab in a real-life cohort of 54 children and/or adolescents with severe plaque psoriasis. Retrospective, multicenter analysis over a 52-week period is discussed in this study. Efficacy was determined by the percentage of patients achieving Psoriasis Area Severity Index (PASI 75) and PASI 90 at weeks 16, 24, and 52 and the response in biologic-naïve versus non-naïve patients. Safety was assessed by the number of patients experiencing at least one adverse event. At week 16, 29.6% of patients achieved a 90% PASI score reduction (PASI 90), while 55.5% of patients achieved a 75% PASI score reduction (PASI 75). Effectiveness was sustained through week 24, since PASI 90 response increased to 55.5% and PASI 75 response increased to 74.0% of patients. The PASI response rates did not differ between biologic-naïve and non-naïve patients. The drug was well tolerated and no serious infections were observed. Adalimumab was effective and safe in this cohort of children with severe plaque psoriasis in a 52-week observation. Effectiveness did not differ between biologic-naïve and non-naïve patients.

Vascular Patterns in Cutaneous Ulcerated Basal Cell Carcinoma: A Retrospective Blinded Study Including Dermoscopy.

The aim of this retrospective study was to determine the type and prevalence of vascular patterns in the ulcerated and non-ulcerated portions of histologically proven basal cell carcinomas (BCCs) and correlate them with other dermoscopic and clinical features, including the clinically supposed diagnosis. Three authors retrospectively collected 156 clinical and 156 dermoscopic digital images of ulcerated BCCs (histologically confirmed); each image was blindly evaluated by 2 other authors, who did not know the histological diagnosis. Seventeen lesions were completely ulcerated, while 139 lesions presented ulcerated and non-ulcerated portions. Correct clinical diagnosis was associated with the type of lesion, in particular 90.6% of partially ulcerated lesions were correctly diagnosed with clinical-dermoscopic examination, compared with 11.8% of totally ulcerated lesions (χ2 = 64.00, p = 0.000). Presence of arborizing pattern in the ulcerated portion was associated with a correct diagnosis (Fisher's exact test, p = 0.015). Correct diagnosis was also associated with absence of dotted pattern in the non-ulcerated area (χ2 = 16.18, p = 0.000); the absence of hairpin (χ2 = 6.08, p = 0.000) and glomerular patterns were associated with correct diagnosis in the ulcerated areas (χ2 = 18.64, p = 0.000). In case of completely ulcerated BCC the clinician lacks the means to correctly identify the correct nature of the lesion, and is driven towards an incorrect diagnostic conclusion.

Eyelid milia en plaque: a treatment challenge with a new CO2 fractional laser.

Milia en plaque (MEP) is an uncommon finding characterized by numerous tiny milia within an erythematous area. Despite its benign and asymptomatic nature, MEP raises cosmetic concerns; moreover, the available treatment modalities for MEP are limited. In view of the few cases described in the literature, no consensus has been reached, with respect to the optimal treatment for MEP, and the choice of therapy should be individualized. We report a case of eyelid milia en plaque successfully treated with a new CO2 fractional laser that is able to ensure superficial ablation of the epidermis remodeling tissue in-depth, with minimal thermal damage and extremely rapid recovery time. The results obtained after only two treatments were good, no scarring or dyschromic changes have been registered. At 1 year, just few recurrent milia were present.

Scalp hair heterochromia in a 5-year-old child: rare somatic mosaicism?

Scalp hair heterochromia presenting in tufts with no underlying skin changes is rare and can be a sign of somatic mosaicism. We describe the case of a healthy 5-year-old boy with this condition.

How to redefine the inframammary fold: the "slingshot" capsular flap.

BACKGROUND: Caudal dislocation of the inframammary fold (IMF) affects cosmetic appearance of the breast. Up until now, few methods have been proposed. The authors introduced a new capsular flap to improve long-lasting results. MATERIALS AND METHODS: Thirty consecutive patients affected by lower dislocation of the IMF have been retrospectively evaluated. Patients have been classified for age, degree of capsular contracture, and IMF dislocation (measured in centimeters). All dislocations have been corrected using a capsular flap cranially advanced on the chest wall in a "slingshot" fashion and anchored to the periosteum of the IV to V rib. RESULTS: No major complications have been registered. In 2 cases, recurrence of IMF dislocation occurred within 15 months. In 3 cases, hypodefinition of the fold in the long-term was recorded. CONCLUSIONS: The slingshot capsular flap seems a valid option to redefine the IMF, improving aesthetic appearance and stability of the result.

Combined use of fractional CO2 laser and radiofrequency waves to treat acne scars: a pilot study on 15 patients.

Fractional laser resurfacing has become an important technique in the management of a number of skin conditions, such as photoaging and scars. A variety of laser wavelengths and delivery systems have been introduced to improve immediate and long-term therapeutic results. The simultaneous emission of CO(2) laser and radiofrequency waves combines epidermal coagulation for a resurfacing effect and dermal denaturization for deeper remodelling. The authors present this new machine together with a preclinical histological study and pilot study on 15 patients suffering from acne scars.

Nutritional impairment of neonates with epidermolysis bullosa: a retrospective study.

BACKGROUND: Epidermolysis bullosa (EB) is a highly invalidating genodermatosis characterized by skin and mucosa fragility and blister-formation caused by mutations of genes encoding components of the cutaneous basement membrane zone. Nutritional impairment is one of the main complications of all forms of EB, having a huge impact on growth, pubertal development, wound healing, resistance to infections and quality of life. METHODS: In our study we have retrospectively evaluated 17 children with EB to define whether nutritional impairment in those patients is already present in the neonatal period. As secondary outcomes we considered nutritional status differences among EB subtypes and relative percentages of underweight infants at birth, first and third month. Moreover, information concerning feeding modality, possible complications were also collected, as well as cutaneous or systemic infections and duration of hospital stay. RESULTS: Our study demonstrated that nutritional impairment of neonates with EB has an early onset since as at first month 35% of patients were below 5th centile for weight-for-age, and 94% were below the 50th percentile. Moreover, the number of infants at one month of life <5th centile for weight-for-age was significantly higher compared to birth. The nutritional status is also heavily related to the occurrence of complications, in particular infections; therefore, the prevention of these complications must play a central role in the treatment of these infants, also to avoid any nutritional impairment. CONCLUSIONS: Nutritional status of neonates with EB seems to be compromised already during the first month of life and it is heavily related to the occurrence of infections; therefore, the prevention of these complications must play a central role in the treatment of these infants, also to avoid any nutritional impairment.

Squamous Cell Carcinoma in Patients with Inherited Epidermolysis Bullosa: Review of Current Literature.

Epidermolysis bullosa (EB) is a group of rare congenital diseases caused by mutations in structural proteins of the dermal/epidermal junction that are characterized by extreme epithelial fragility, which determines the formation of bullae and erosions either spontaneously or after local mechanical traumas. In EB patients, skin fragility leads to many possible complications and comorbidities. One of the most feared complications is the development of cutaneous squamous cell carcinomas (SCCs) that particularly in the dystrophic recessive EB subtype can be extremely aggressive and often metastatic. SCCs in EB patients generally arise more often in the extremities, where chronic blisters and scars are generally located. SCCs represent a big therapeutic challenge in the EB population. No standard of care exists for the treatment of SCC in these patients, and therapy is based on small case studies. Moreover, the pathogenesis of cSCC in EB patients is still unclear. Many theories have been indeed postulated in order to explain why cSCC behaves so much more aggressively in EB patients compared to the general population. cSCC in EB seems to be the result of many complex interactions among cancer cells, skin microenvironment, susceptibility to DNA mutations and host immune response. In this review, we analyze the different pathogenetic mechanisms of cSCC in EB patients, as well as new therapies for this condition.

Immune Disregulation in Cutaneous Squamous Cell Carcinoma of Patients with Recessive Dystrophic Epidermolysis Bullosa: A Single Pilot Study.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is one of the most devastating complications of recessive dystrophic epidermolysis bullosa (RDEB). We recently demonstrated a reduction in immune cell peritumoral infiltration in RDEB patients with cSCC, together with a reduction in CD3+, CD4+, CD68+ and CD20 lymphocytes as compared to primary and secondary cSCC in patients without RDEB. Recently, new molecules, such as high mobility group box 1 (HMGB1), T cell immunoglobulin, mucin domain 3 (TIM-3) and Heme oxygenase-1 (HO-1), have been shown to play a role in antitumoral immunity. OBJECTIVE: Patients with RDEB are known to be at increased risk of developing skin cancers, including the dreaded squamous cell carcinoma of the. Tendentially, cSCCs that arise in the context of EBDR are more aggressive and lead to statistically significant bad outcomes compared to cSCCs developed on the skin of patients without EBDR. In an attempt to study the microenvironment of these lesions, we conducted an immunohistochemical analysis study of proteins that could be actively involved in the genesis of this type of malignant neoplasms. METHODS: In this retrospective study, the OH1-HMGB1-TIM3 activation axis, as correlated to the T lymphocytes cell count, was assessed in biopsy samples from 31 consecutive cases consisting of 12 RDEB patients with cSCC, 12 patients with primary cSCC and 7 RDEB patients with pseudoepitheliomatous cutaneous hyperplasia. Parametric Student's t-test was applied for normally distributed values, such as CD4+ and CD8+, and non-parametric Mann-Whitney test for non-normally distributed values, such as HMGB-1, TIM-3 and HO-1. RESULTS: In RDEB patients with cSCC and with pseudoepitheliomatous hyperplasia, the expression of CD4 T helper lymphocytes was lower than in the peritumoral infiltrate found in primary cSCC. CD8 cytotoxic T lymphocytes were increased in primary cSCC compared to the other two groups. An increased HMGB1 expression was evident in both primary and RDEB cSCC. TIM3 expression was higher in RDEB patients with cSCC compared to the other two groups. A significantly reduced immunohistochemical expression of HO-1 was evident in the tumoral microenvironment of cSCC-RDEB as compared to primary cSCC. CONCLUSIONS: These data suggest that a reduced immune cell peritumoral infiltration in RDEB patients could be responsible, in the complexity of the mechanisms of carcinogenesis and host response, of the particular aggressiveness of the cSCC of RDEB patients, creating a substrate for greater local immunosuppression, which, potentially, can "open the doors" to development and eventual metastasis by this malignant neoplasm.

Self-inflicted pathological cutaneous disorders. Part II.

Self-inflicted skin disorders are artefact diseases inflicted by the use of multiple different means, for various different purposes. They account for about 2% of dermatology patient visits, and include disorders with a denied or hidden pathological behavior (factitious disorders) and disorders with a non-denied and non-hidden pathological behavior (compulsive disorders). In turn, factitious skin disorders are subdivided into 2 groups: factitious disorders without an external incentive (considered in a preceding work) and factitious disorders with external incentives. In the second eventuality, the simulator is motivated by illicit intent, wishing to evade civil duties or a prison sentence, for instance, or to exploit situations of an occupational nature, and is fully aware of his action and his intention. Apart of the two groups of pathomimic artefacts and malingering, some self-inflicted dermatoses are due to behavioral disorders involving compulsive habits (tics, psychological excoriations). The great majority of subjects suffering from the latter disturbances are quick to confess their urge to self-inflict lesions. The management, including both psychiatric and dermatological assessment, concludes this second part of the work regarding the self-inflicted cutaneous diseases.