The Effect of the COVID-19 Lockdown on Melanoma Diagnosis in Italy.

The coronavirus disease 2019 (COVID-19) pandemic has led to lockdowns for much of the world. In Italy, all health procedures not directly related to COVID-19 were reduced or suspended, thus limiting patient access to hospitals. Any delay in cancer treatment presents the additional risk of tumors progressing from being curable to incurable. Specifically, melanoma survival rate strictly depends on tumor thickness, which, in turn, is a function of time. To estimate the impact on melanoma progression caused by the reduction in dermatologic services during the COVID-19 lockdown, a retrospective observational cohort study was conducted. This study was designed to compare the clinical and histologic characteristics of the primary melanomas removed in the first 2 months after the end of the lockdown (May-July 2020) in 12 Italian centers characterized by different COVID-19 case frequencies. The control group was represented by the melanomas removed during the same period in the previous 3 years. Overall, 1,124 melanomas were considered: 237 as part of the study group and 887 from the control group (average, 295), with a 20% reduction. Breslow thickness, as well as high-risk histotypes and melanomas with vertical growth, increased for all melanomas. Ulcerated and high mitotic index melanomas increased, particularly in northern Italy. In Italy, the lockdown led to a significant worsening of melanoma severity, causing a staging jump, with a consequent worsening of outcomes.

Mental Health Consequences of the COVID-19 Pandemic Long-Term Exposure in Italian Dermatologists.

The present study aimed at assessing the consequences of prolonged exposure to COVID-19 distress on mental health in non-frontline health care workers. For this purpose, we have conducted a survey on 425 Italian dermatologists, in the period February-March 2021. The psychopathological symptoms, depression, anxiety, post-traumatic stress symptoms (PTSD), as well as resilience, have been evaluated. The main factors that influence the physician's psychological health have been also investigated. Our study showed that the physicians older than 40 years, as well as those who lived this period in company, reported more personal resources, better managing the distress. Resilience, COVID-19 beliefs, COVID-19 working difficulties, and age were the common predictors of the severe psychopathological symptoms. An interesting result is that the lower level of resilience was the most powerful predictor of a more severe depression, as well as of a higher severity of generalized anxiety disorder, but not of COVID-19 PTSD. The fear of COVID-19 was the most powerful predictor of COVID-19 PTSD. Home conditions and previous SARS-CoV2 infection constituted significant predictors of severe depressive symptoms, but not of anxiety and COVID-19 PTSD. These results are useful in a better understanding of protective and risk factors involved in COVID-19 long-term distress exposure.

Combined laser assisted treatment for permanent hair removal for skin types I-V with Alexandrite 755 nm and ND:YAG 1064 nm lasers.

This retrospective cohort study regarding hair removal procedures considers all the data collected in three different clinical centers from 2017 to 2019. The device used to perform the treatments was composed of an Alexandrite 755 nm and an Nd:YAG 1064 nm laser, that delivered both wavelengths in a blended simultaneous emission (Thunder MT, Quanta System, Samarate, Italy). The improvement evaluated after five sessions of treatment by an external referee was: 83.0% for armpits, 82.1% for the bikini line, 82.2% for legs, 79.6% for thorax, and 81.6% for the back. The collected temporary skin reaction data reported in this study were all acceptable and transitory resolving in less than 1 week. The level of erythema and perifollicular edema were all signs of the reached treatment endpoint. First degree burns, hyper, and hypopigmentation were also reported in a few cases but these, all resolved before the follow-up visit without any permanent skin effects. No adverse effects were thus reported to have happened. This retrospective study demonstrates the efficacy of combining Alexandrite and Nd:YAG lasers in a mixed modality with simultaneous emission. This technology permitted to treat patients with skin types I-V without any reported permanent side effects and with a high pain tolerability compared to the use of Nd:YAG in single mode.

Skin vascular lesions: A new therapeutic option with sequential laser-assisted technique.

Treatment of skin unaesthetic vascular lesions is still suboptimal. In this article, we present a multicenter study evaluating the efficacy and safety of the sequential 755 nm Alexandrite and 1064 nm ND:YAG lasers for the treatment of acquired and congenital vascular lesions of the skin. A total of 171 patients were included in the study (141 female and 30 male), median age 38, skin type from I to IV. Numbers of patients categorized for treated disease: 22 spider angiomas, 67 facial telangiectasia/spider veins, 58 leg telangiectasia/reticular leg veins, 24 port wine stains (PWS). Of those lesions 30.7% was on legs, 63.7% on face (6.7% on forehead, 10.1% on temples, 21.7% on cheeks, 25.2% on nose, 1.7% on chin) and 5.6% on chest. Spider angiomas required from 1 to 3 treatments. Facial telangiectasias had been treated from 1 to 4 times. Leg telangiectasias needed from 2 to 6 treatment sessions. Regarding PWS, it takes from 6 to 9 laser treatment to reach the clearance of the lesion. All the vascular disorders treated showed marked improvement while side effects were limited to low pain sensation and transitory fenomena. This sequential treatment is an effective, safe, and new approach for unaesthetic skin vascular lesions.

"Drug-resistant granuloma faciale": treatment with carbon dioxide-GaAs laser.

Granuloma faciale (GF), also known as "eosinophilic granuloma," is a rare benign leukocytoclastic vasculitis which most commonly occurs on the face of middle-aged Caucasian males. Clinically, GF appears as single or multiple, slowly growing, reddish-brown papules, nodules or plaques which may be cosmetically unpleasant. Its pathogenesis is unknown and GF is notoriously resistant to treatments. Both medical (dapsone, colchicine, gold injections, isoniazid, clofazimine, corticosteroids, psoralen ultraviolet radiation, and topical tacrolimus) and surgical therapies (excision, graft, dermabrasion, argon laser, carbon dioxide laser, pulsed dye laser, cryotherapy, and electrosurgery) have been used for GF but no effective treatment has yet been found. Furthermore, the typical facial location of GF requires an acceptable cosmetic result. We report two cases of drug-resistant GF which were successfully treated with laser vaporization combining two different wavelengths: carbon dioxide (CO2 ) 10,600 nm and GaAs 1540 nm.

Objective melanoma progression.

BACKGROUND/PURPOSE: Many aspects of the natural history of malignant melanoma (MM) are still unclear, specifically its appearance at onset and particularly how it changes in time. The purpose of our study was to retrospectively determine objective changes in melanoma over a 3-24-month observation period. MATERIALS AND METHODS: Our study was carried out in two Italian dermatology centers. Digital dermoscopy analyzers (DB-Mips System) were used to retrospectively evaluate dermoscopic images of 59 MM (with no initial clinical aspects suggesting melanoma) under observation for 3-24 months. The analyzer evaluates 49 parameters grouped into four categories: geometries, colors, textures and islands of color. Multivariate analysis of variance for repeated measures was used to evaluate the statistical significance of the changes in the digital dermoscopy variables of melanomas. RESULTS: Within-lesion analysis indicated that melanomas increased in dimension (Area, Minimum, and Maximum Diameter), manifested greater disorganization of the internal components (Red, Green and Blue Multicomponent, Contrast, and Entropy) and increased in clusters of milky pink color (Light Red Area). CONCLUSION: Analysis of the parameters of our model and statistical analysis enabled us to interpret/identify the most significant factors of melanoma modification, providing quantitative insights into the natural history of this cutaneous malignancy.

Evaluation of cutaneous melanoma thickness by digital dermoscopy analysis: a retrospective study.

Digital dermoscopy analysis (DDA) exploits computerized analysis of digital images and offers the possibility of parametric analysis of morphological aspects of pigmented skin lesions by means of integration with dedicated software. We conducted a study by DDA in 141 melanomas, with the aim assessing whether the numerical variables extrapolated by univariate logistic analysis could be used in a system of multivariate analysis to predict melanoma thickness before surgery. Melanoma images were evaluated for 49 DDA parameters. Logistic analysis was conducted to identify statistically significant variables. The leave-one-out method was used to evaluate the predictive representations of rules for stepwise logistic classification. The percentage of correctly classified cases was calculated by a classification matrix. Melanomas less than 1 mm had a smaller area, faded borders and were more symmetrical than melanomas greater than 1 mm. The latter had a bluer colour and more random disposition of elements. The accuracy was 86.5%. Specifically, 97 of 108 thin melanomas (specificity 89.8%) and 25 of 33 thick melanomas (sensitivity 75.7%) were correctly classified. In conclusion, the predictive value of DDA for melanoma thickness was quite good. Moreover, DDA allowed us to know objectively those dermoscopic features important in the differentiation between thick and thin melanoma. However, further studies should be performed in a prospective setting before the clinical application.

Objective follow-up of atypical melanocytic skin lesions: a retrospective study.

Various authors have suggested that information from longitudinal observation (follow-up) of dynamic changes in atypical melanocytic pigmented skin lesions (MPSL) could enable identification of early malignant melanoma escaping initial observation due to an absence of specific clinical and dermoscopic features. The aim of our retrospective study was to determine the existence of numerical variables regarding changes in MPSL that could be useful to differentiate early melanomas and atypical nevi. The study was carried out in two Italian dermatology Centres. Digital dermoscopy analyzers (DB-Mips System) were used to evaluate dermoscopic images of 94 equivocal pigmented skin lesions under observation for 6-12 months and then excised because of changes across time (29 melanomas and 65 nevi). The analyzer evaluates 49 parameters grouped into four categories: geometries, colours, textures and islands of colour. The ROC curve designed on the 49 digital dermoscopy analysis parameters showed good accuracy. At sensitivity (SE) = specificity (SP), it correctly classified 89.3% of cases. When objective pigmented skin lesion parameters were considered together with their objective changes over 6-12 months, a decisive increase in discrimination capacity was obtained. At SE = SP accuracy was 96.3%. Analysis of the parameters of our model and statistical analysis enabled us to interpret/identify the most significant factors of modification and differentiation of lesions, providing quantitative insights into the diagnosis of equivocal MPSL and demonstrating the utility of objective/numerical follow-up.

Use of donor bone marrow mesenchymal stem cells for treatment of skin allograft rejection in a preclinical rat model.

Recent studies indicate that mesenchymal stem cells (MSC) exhibit a degree of immune privilege due to their ability to suppress T cell mediated responses causing tissue rejection; however, the impact of allogeneic MSC in the setting of organ transplantation has been poorly investigated so far. The aim of our study was to evaluate the effect of intravenous donor MSC infusion for clinical tolerance induction in allogeneic skin graft transplantations in rats. MSC were isolated from Wistar rats and administered in Sprague-Dawley rats receiving Wistar skin graft with or without cyclosporine A (CsA). Graft biopsies were performed at day 10 post transplantation in all experimental groups for histological and gene expression studies. Intravenous infusion with donor MSC in CsA-treated transplanted rats resulted in prolongation of skin allograft survival compared to control animals. Unexpectedly, donor MSC infusion in immunocompetent rats resulted in a faster rejection as compared to control group. Cytokine expression analysis at the site of skin graft showed that CsA treatment significantly decreased pro-inflammatory cytokines IFN-gamma and IL-2 and reduced TNF-alpha gene expression; however, the level of TNF-alpha is high in MSC-treated and not immunosuppressed rats. Results of our study in a rat tissue transplantation model demonstrated a possible immunogenic role for donor (allogeneic) MSC, confirming the need of adequate preclinical experimentation before clinical use.

Thalidomide in the treatment of Kaposi's sarcoma.

BACKGROUND: Kaposi's sarcoma (KS) is a lymphangioproliferative tumour. Therapy of KS depends on the characteristics of the disease, especially area and growth rate of lesions, and patient condition. Currently symptomatic resectable lesions are excised, whereas more advanced disease and unresectable lesions are treated with radiotherapy. If a large area or internal organs are affected or other treatments fail, chemotherapy is used. Recently some authors have reported their encouraging experience in the use of thalidomide in patients with AIDS-related KS. OBJECTIVE: To evaluate the efficacy of thalidomide in 3 patients with non-AIDS-related KS. METHODS: Two patients with classic widespread cutaneous and 1 with iatrogenic cutaneous and visceral KS were treated with thalidomide (100 mg/day) for 12 months. RESULTS: In all 3 patients partial remission was evident after 4 months of thalidomide therapy; in 2 out of 3 complete remission was achieved after 12 months of treatment. CONCLUSIONS: Our results seem to confirm the utility of thalidomide in the treatment of non-AIDS-related KS.

A case of idiopathic granulomatous cheilitis and vulvitis.

A 36-year-old woman presented with chronic recurring dermatitis of the vulva, perineum, and lips. The genital lesions had a 3-year history and were associated with slight pruritus and occasional pain. The lesions of the upper lip had a history of 6 months. The patient had been treated with cycles of antimycotics and topical steroids which only partially controlled the symptoms during treatment. Dermatologic examination showed erythematous, infiltrative dermatitis with edema of the labia majora and persistent edema of the upper lip (Fig. 1a,b). Routine blood chemistry, urine analysis, and chest X-ray were normal. Microscopic examination and cultures of vaginal swabs did not reveal any pathogenic bacteria or fungi. Histologic examination of a biopsy of vulval lesional skin showed lichenoid lymphocytic infiltration of the papillary dermis and small, nonnecrotic epithelioid granulomas in the deep dermis (Fig. 1c,d). No microorganisms, including acid-fast bacilli or fungi, were identified. Culture was negative for fungi. Polymerase chain reaction was negative for the mycobacterial genome. Histologic examination of a biopsy from the upper lip showed similar results. The pathology reports of both regions were compatible with a diagnosis of granulomatous cheilitis and vulvitis. To investigate concomitant asymptomatic inflammatory bowel disease, the patient underwent colonoscopy with retrograde ileoscopy and gastroscopy, which were both negative. The patient refused radiographic examination of the small intestine with a barium meal. The patient was treated with systemic metronidazole (500 mg/day). After 6 months of therapy, the upper lip showed significant improvement and erythema and desquamation in the genital area showed slight improvement, but genital edema was unaffected.

Melanocytic skin lesions and pregnancy: digital dermoscopy analysis.

BACKGROUND: Very few studies have tried to clarify how pregnancy influences the morphology of pigmented skin lesions (PSL). Our purpose was to objectively determine, by digital dermoscopy analysis (DDA), any dermoscopic changes of acquired melanocitic nevi during pregnancy and after 1 year from delivery. METHODS: Thirty-five healthy pregnant women and 35 age-matched female controls were enrolled in the study. Nevi of pregnant women were analysed by DDA between 5 and 8 weeks of pregnancy, between 39 and 41 weeks of pregnancy and 12 months after delivery. Nevi of control women were analysed by DDA in a month of the year matching the period of recruitment of pregnant women and 21 months later. RESULTS: Multivariate analysis of variance (manova) for repeated measures revealed that dermoscopic variables SKIN-GREEN-AVERAGE, SKIN-BLUE-AVERAGE and CONTRAST changed during pregnancy but returned to non-significant values after a year from delivery. The variable ENTROPY showed significant differences between initial evaluation and 1 year after delivery. Finally, the variable VARIANCE OF BORDER GRADIENT showed a significant difference between the first and the last evaluations, in both pregnant and control subjects. CONCLUSIONS: The study showed that pregnancy leads to significant modifications in PSL, especially with regard to pigment network, globules and architectural order or disorder.

Prevalence of skin allograft discards as a result of serological and molecular microbiological screening in a regional skin bank in Italy.

BACKGROUND: Postmortem skin is widely used in the treatment of patients with severe burns. Skin specimens must be screened for transmissible agents including human immunodeficiency virus (HIV), hepatitis B (HBV) and C (HCV) virus, human T-cell lymphotropic virus (HTLV), cytomegalovirus (CMV) and Treponema pallidum. METHODS: Four hundred and sixty-one cadaveric donors underwent serological and molecular microbiological (polymerase chain reaction, PCR) screening at Siena Skin Bank between 2000 and 2004. RESULTS: 74/461 donors (16.1%) were found ineligible under current regulations. CONCLUSIONS: These results are interesting in a local context and underline the importance of screening involving both routine serological procedures and molecular microbiological investigation. The latter has not been uniformly introduced in many countries and very limited data is available to assess its cost-benefit ratio in the field of skin donor screening.

Subcutaneous panniculitis lymphoma: erythema nodosum-like.

We report the case of a patient who presented with painful nodular subcutaneous lesions on the lower limbs and episodes of high temperature (> 39.5 degrees C). Histologic examination and immunohistochemical study of a biopsy specimen from a nodular lesion were consistent with the diagnosis of subcutaneous panniculitis-like T-cell lymphoma, a rare form of non-Hodgkin lymphoma. Diagnosis is made particularly difficult, especially in the early stages, by nonspecific clinical features shared by many types of panniculitis. Therefore, it seems advisable to consider the possibility of this type of lymphoma in all cases of panniculitis and to perform careful and continuous follow-up of all cases in which a clear diagnosis is not formulated at the outset, with regular repetition of skin biopsies at appropriate intervals.

Other uses of homologous skin grafts and skin bank bioproducts.

The main use of homologous skin grafts or grafts of related bioproducts is in the treatment of severe burns. However, various new clinical and experimental sectors, in which this type of skin substitute can be useful, have recently emerged. The main new clinical indications for skin allografts include: skin loss, surgical wounds and bullous diseases. In these fields donor skin can be used for different purposes: as a physiological biological dressing to control pain and protect deep structures such as tendons, bones, cartilage and nerves, and to promote reepithelization with a significant reduction in healing time, and as skin substitute with dermal tissue to guide repair and make it as physiological as possible. In particular, skin bank bioproducts are currently used in the treatment of several conditions such venous and arterial leg ulcers, pressure ulcers, diabetic foot ulcers, pyoderma gangrenosum, post traumatic lesions, Mohs surgery, reconstructive surgery, wound cover in critical areas, aesthetic surgery, congenital epidermolysis bullosa and Lyell's syndrome. Skin bank bioproducts have also been used for experimental indications, to study in vitro toxicology and in vitro skin biology. Recently the demonstration that de-epidermized dermis (DED) has all the characteristics of an excellent dermal substitute into which various types of cells can be introduced and made to develop, opens exciting new possibilities of research in the field of wound healing and tissue engineering. Our preliminary observations seems to indicate that CD 34+ stem cells from umbilical cord blood can survive in DED and in a few weeks populate collagen bundles. The observation of tubular structures without lumina close to collagen bundles as well as clusters of epithelioid or fibroblast-shaped cells may represent aspects of differentiation of CD 34+ stem cells. More detailed and sophisticated studies are clearly needed to answer all the questions that these initial observations pose. Anyway the 3-dimensional model proposed seems to be suitable for the study of the behaviour of peripheral CD 34+ and perhaps also other types of stem cells in 3-dimensional dermal matrix.

Acroangiodermatitis (pseudo-Kaposi sarcoma) associated with verrucous hyperplasia induced by suction-socket lower limb prosthesis.

Increasing use of suction-socket lower limb prostheses has been associated with an increased frequency of dermatological manifestations, linked to the fact that the skin of the amputation stump must adapt to an entirely new environment. In particular, verrucous hyperplasia and rare cases of acroangiodermatitis (pseudo-Kaposi sarcoma) have been described. We report a case of amputation stump dermatitis, clinically resembling verrucous hyperplasia, but with predominant histological aspects of acroangiodermatitis in a patient with a suction-socket lower limb prosthesis.