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Background Timely recognition of malignant melanoma (MM) is challenging for dermatologists worldwide and represents the main determinant for mortality. Dermoscopic examination is influenced by dermatologists’ experience and fails to achieve adequate accuracy and reproducibility in discriminating atypical nevi (AN) from early melanomas (EM). Objective We aimed to develop a Deep Convolutional Neural Network (DCNN) model able to support dermatologists in the classification and management of atypical melanocytic skin lesions (aMSL). Methods A training set (630 images), a validation set (135) and a testing set (214) were derived from the idScore dataset of 979 challenging aMSL cases in which the dermoscopic image is integrated with clinical data (age, sex, body site and diameter) and associated with histological data. A DCNN_aMSL architecture was designed and then trained on both dermoscopic images of aMSL and the clinical/anamnestic data, resulting in the integrated “iDCNN_aMSL” model. Responses of 111 dermatologists with different experience levels on both aMSL classification (intuitive diagnosis) and management decisions (no/long follow-up; short follow-up; excision/preventive excision) were compared with the DCNNs models. Results In the lesion classification study, the iDCNN_aMSL achieved the best accuracy, reaching an AUC = 90.3 %, SE = 86.5 % and SP = 73.6 %, compared to DCNN_aMSL (SE = 89.2 %, SP = 65.7 %) and intuitive diagnosis of dermatologists (SE = 77.0 %; SP = 61.4 %). Conclusions The iDCNN_aMSL proved to be the best support tool for management decisions reducing the ratio of inappropriate excision. The proposed iDCNN_aMSL model can represent a valid support for dermatologists in discriminating AN from EM with high accuracy and for medical decision making by reducing their rates of inappropriate excisions.

Background Few and small studies have described the management of immunomodulant/immunosuppressive therapies or phototherapy in atopic dermatitis (AD) patients during coronavirus disease 2019 (COVID‐19) pandemic. Methods A national registry, named DA‐COVID‐19 and involving 35 Italian dermatology units, was established in order to evaluate the impact of COVID‐19 pandemic on the management of adult AD patients treated with systemic immunomodulant/immunosuppressive medications or phototherapy. Demographic and clinical data were obtained at different timepoints by teledermatology during COVID‐19 pandemic, when regular visits were not allowed due to sanitary restrictions. Disease severity was assessed by both physician‐ and patient‐reported assessment scores evaluating itch intensity, sleep disturbances, and AD severity. Results A total of 1831 patients were included, with 1580/1831 (86.3%) continuing therapy during pandemic. Most patients were treated with dupilumab (86.1%, 1576/1831) that was interrupted in only 9.9% (156/1576) of cases, while systemic immunosuppressive compounds were more frequently withdrawn. Treatment interruption was due to decision of the patient, general practitioner, or dermatologist in 39.9% (114/286), 5.6% (16/286), and 30.1% (86/286) of cases, respectively. Fear of increased susceptibility to SARS‐CoV‐2 infection (24.8%, 71/286) was one of the main causes of interruption. Sixteen patients (0.9%) resulted positive to SARS‐CoV‐2 infection; 3 of them (0.2%) were hospitalized but no cases of COVID‐related death occurred. Conclusions Most AD patients continued systemic treatments during COVID pandemic and lockdown period, without high impact on disease control, particularly dupilumab‐treated patients., Among 1831 studied AD patients, 86.1% were treated with dupilumab. Patients continuing therapy experienced a marked reduction of disease severity during pandemic. The causes of treatment interruption included: fear of increased susceptibility to SARS‐CoV‐2 infection (24.8%), occurrence of comorbidities (5.9%), age above 60 years (5.2%), SARS‐CoV‐2 infection (2.8%), close contact with SARS‐CoV‐2‐positive subject (2.4%), other reasons, for example, inability to maintain drug supply, non‐medical/unspecified causes (58.7%).

Background The susceptibility of patients with chronic plaque psoriasis and the risks or benefits related to the use of biological therapies for COVID-19 are unknown. Few data about prevalence, clinical course and outcomes of COVID-19 among psoriatic patients were reported. The aims of this study were 1) to assess the prevalence and severity of COVID-19 in psoriatic patients treated with biologic agents during the first phase of the emergency (22 February to 22 April 2020) in Italy, and 2) to report the clinical outcomes of patients who have been exposed to individuals with confirmed SARS-CoV-2 infection. Methods Patients with moderate-to-severe chronic plaque psoriasis, aged ≥18 years and undergoing treatment with biologic agents as of 22 February 2020, were eligible to be included in PSO-BIO-COVID study. Demographic and clinical characteristics of patients using any biologic for psoriasis treatment between 22 February and 22 April 2020 were registered. For all confirmed or suspected cases of COVID-19, data about concomitant disease, ongoing therapies, and comorbidities were also reported. Results A total of 12,807 psoriatic patients were included in the PSO-BIO-COVID study. In this cohort twenty-six patients (0.2%) had a swab confirmation of SARS-CoV-2 infection. Eleven patients required hospitalization and two died. 125 of 12807 patients (1.0%) with exposure to a patient with COVID-19 under quarantine or active health surveillance, were reported. Conclusion The incidence of COVID-19 observed in our cohort of psoriatic patients (0.2%) is similar to that seen in the general population (0.31%) in Italy. However, the course of the disease was mild in most patients. Biological therapies may likely lessen "cytokine storm" of COVID-19, which sometimes lead to multiple organ failure, ARDS, and death.

This work explores how comic-based digital storytelling can support children and teachers in combining foreign language and content teaching in the Content and Language Integrated Learning (CLIL) framework. In particular, we focus on investigating three specific aspects: (1) the use of digital storytelling in terms of collaboration, engagement and ease of use, (2) the adoption of comic-based digital storytelling in the CLIL framework, and (3) the benefits and limitations in using digital storytelling in comparison to a paper-based version. In order to investigate these aspects, we develop a case study in a primary school in Italy. A class of 18 children and 2 teachers used a digital tool, named ComicsCLIL, with the aim of creating digital narratives in the CLIL framework. The results provide some evidences that comicbased digital storytelling can be a beneficial educational tool for approaching CLIL lessons. It emerged, in fact, that digital storytelling, as supported by ComicsCLIL, can facilitate this practice by being engaging, easy to use, fully educational while considering the collaborative aspect.

BACKGROUND Sleep disturbances are common in patients with atopic dermatitis (AD). Considering their relevant burden on health, routine screening of sleep disturbances seems to be very useful in AD adults management. However, few studies have evaluated the association between sleep disturbances and AD in adults and real-life data are lacking. The aim is to assess the effect of treatment with dupilumab on sleep disturbances in adult patients with severe atopic dermatitis. METHODS Retrospective, multicenter study including patients (age≥18 yr.s) with severe atopic dermatitis who were treated with dupilumab for at least 8 months from January 2019 to January 2020. Patients were evaluated three times: at treatment initiation (T0) and at 4 (T4) and 8 months (T8) from the start of treatment. At each visit disease activity was assessed by severity score (Eczema Area and Severity Index, EASI), patient-reported outcomes (Pruritus Numerical Rating Scale, NRS, Dermatology Life Quality Index,DLQI, and Pittsburgh Sleep Quality Index, PSQI). Kolmogorov-Smirnov test was performed to evaluate the normality distribution, Bartlett's test for homoscedasticity. Since the assumptions were met, ANOVA for repeated measures was performed to evaluate the mean difference of PSQI, EASI, DLQI and Pruritus NRS between baseline, 4th month and 8th month. In addition, Chi-square for Trend test was performed to evaluate the increasing/decreasing prevalence of poor sleepers. RESULTS A total of 36 patients (15 females and 21 males) with a mean age of 42.5±14.3 (range 20-67) were included in the study. The mean score for PSQI at TO was 9.0 ±3.6. At week 16 (T4) the mean score for PSQI was 4.92±2.99 and at week 32 (T8), the mean score for PSQI was 4.3± 3.0. EASI, NRS pruritus and DLQI significantly improved during follow up (p

Aicardi-Goutieres syndrome (AGS) is a rare autosomal recessive disorder first described by Jean Aicardi and Francoise Goutieres in 19841 . Given the elevated serum and cerebrospinal fluid (CSF) levels of interferon-α (IFNα), it belongs to the group of type 1 interferonopathies2 . Cutaneous manifestations are the most frequent extra neurologic findings and include chilblain-like lesions (CLL), acrocyanosis, distal tapering of digits, and nail abnormalities3-5 .

Varicella-like exanthem as a specific COVID-19-associated skin manifestation: Multicenter case series of 22 patients

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is creating an unprecedented global public health emergency with the continuous growth of infected individuals worldwide. Italy was one of the first European country to face the first wave of infection outside mainland China. The first case of COVID-19 was confirmed in Lombardy on February 20th , 2020, and subsequently, a rapid increase in the number of detected cases was observed, spreading through Italy and the rest of Europe.3 As of April 22nd , confirmed COVID-19 cases in Italy were 183,957.

Background Although live and teledermoscopic examination has been successfully used to achieve non-invasive diagnosis of melanocytic skin lesions (MSLs), early melanoma (EM) and atypical nevi (AN) continue to be a challenge, and none of the various algorithms proposed have been sufficiently accurate. We designed a scoring classifier diagnostic method, the iDScore that combines clinical data of the patient with dermoscopic features of the MSL. Objective To test the accuracy of the iDScore in differentiating EM from AN in a teledermoscopy setting and to compare it with intuitive diagnosis, the ABCD rule and the seven-point checklist. Materials and methods A dedicated teledermoscopy web platform was designed. This involved the following: (i) collecting a large integrated clinical-historical-dermoscopic data set of difficult MSLs from eight European dermatology centres; (ii) online testing, education and training in using the iDScore. A total of 904 images were combined with age, sex, lesion diameter and body site data and evaluated on the platform by 111 participants with four levels of skill in dermoscopy. Each testing session consisted of 30 blind cases to examine consecutively by the above four methods. 'Management decisions' and personal participant data were also recorded. Results iDScore-aided diagnosis achieved satisfactory diagnostic accuracy for all lesions, irrespective of centre of affiliation, showing an average AUC of 0.776 in all participant testing sessions. All skill groups improved their accuracy by 10-16% with respect to intuitive diagnosis and the other methods, showing high concordance and avoiding wrong management decisions. Conclusion We demonstrated the validity of the iDScore method for managing suspicious MSLs in a large multicentric data set and a teledermoscopic setting. The platform designed for the iDScore project provides ready support for physicians of any dermoscopy skill level and is useful for education and training.

BACKGROUND: Dermoscopy is a widely used technique, recommended in clinical practice guidelines worldwide for the early diagnosis of skin cancers. Intra-European disparities are reported for early detection and prognosis of skin cancers, however, no information exists about regional variation in patterns of dermoscopy use across Europe. OBJECTIVE: To evaluate the regional differences in patterns of dermoscopy use and training among European dermatologists. MATERIALS & METHODS: An online survey of European-registered dermatologists regarding dermoscopy training, practice and attitudes was established. Answers from Eastern (EE) versus Western European (WE) countries were compared and their correlation with their respective countries' gross domestic product/capita (GDPc) and total and government health expenditure/capita (THEc and GHEc) was analysed. RESULTS: We received 4,049 responses from 14 WE countries and 3,431 from 18 EE countries. A higher proportion of WE respondents reported dermoscopy use (98% vs. 77%, p

PRUNE1-related disorders manifest as severe neurodevelopmental conditions associated with neurodegeneration, implying a differential diagnosis at birth with static encephalopathies, and later with those manifesting progressive brain damage with the involvement of both the central and the peripheral nervous system.Here we report on another patient with PRUNE1 (p.Asp106Asn) recurrent mutation, whose leukodystrophy, inferior olives hyperintensity, and macrocephaly led to the misleading clinical suspicion of Alexander disease. Clinical features, together with other recent descriptions, suggest avoiding the term “microcephaly” in defining this disorder that could be renamed “neurodevelopmental disorder with progressive encephalopathy, hypotonia, and variable brain anomalies” (NPEHBA).

BACKGROUND Reflectance confocal microscopy (RCM) is particularly suitable for the study of skin ageing because it provides nearly histological information in vivo and non-invasively. However, there are no studies that evaluated RCM skin features of a large population older than 70 years. OBJECTIVES The aim of our investigation was to study age-related skin changes in an elderly population by RCM and to evaluate their topographical and gender differences. METHODS We obtained RCM images of photoprotected (volar arm) and chronic (face) and intermittently photoexposed (dorsal forearm) body sites of 209 volunteers (105 women and 104 men, mean age: 77.5, range 74-81 years). 15 previously reported and new RCM parameters related to skin ageing were assessed. RESULTS Photoexposed sites had thicker suprapapillary epidermis, more linear, distant and thin furrows, higher presence of mottled pigmentation, polycyclic papillae and coarse and huddled collagen and lower presence of dermal papillae than the photoprotected site. Irregular honeycomb pattern was not higher in photoexposed sites, indicating that it is probably more dependent on intrinsic ageing. Two ageing scores defined for facial skin ageing (epidermal disarray score and epidermal hyperplasia score) were found useful for the identification of photoageing. Gender differences only concerned some RCM parameters (i.e. thickness of different layers of the epidermis, furrows and collagen score) and some body sites, in line with the fact that women and men of our cohort had no major differences in clinically visible skin ageing. CONCLUSIONS Our study confirmed that RCM is a powerful non-invasive technique to microscopically quantify ageing signs and our observations contribute to highlight the differences between intrinsic and extrinsic ageing.

Ophthalmologists usually evaluate melanocytic conjunctival tumor on clinical and slit-lamp examination and perform biopsies in cases of malignancy suspicion. However, differential diagnosis can be ...

Autosomal recessive spastic paraplegia 52 is caused by biallelic mutations in AP4S1 which encodes a subunit of the adaptor protein complex 4 (AP‐4). Using next‐generation sequencing, we identified three novel unrelated SPG52 patients from a cohort of patients with cerebral palsy. The discovered variants in AP4S1 lead to reduced AP‐4 complex formation in patient‐derived fibroblasts. To further understand the role of AP4S1 in neuronal development and homeostasis, we engineered the first zebrafish model of AP‐4 deficiency using morpholino‐mediated knockdown of ap4s1. In this model, we discovered several phenotypes mimicking SPG52, including altered CNS development, locomotor deficits, and abnormal neuronal excitability.

Monoallelic variants in the KIF1A gene are associated with a large set of clinical phenotypes including neurodevelopmental and neurodegenerative disorders, underpinned by a broad spectrum of central and peripheral nervous system involvement. In a multicenter study conducted in patients presenting spastic gait or complex neurodevelopmental disorders, we analyzed the clinical, genetic and neuroradiological features of 28 index cases harboring heterozygous variants in KIF1A. We conducted a literature systematic review with the aim to comparing our findings with previously reported KIF1A-related phenotypes. Among 28 patients, we identified nine novel monoallelic variants, and one a copy number variation encompassing KIF1A. Mutations arose de novo in most patients and were prevalently located in the motor domain. Most patients presented features of a continuum ataxia-spasticity spectrum with only five cases showing a prevalently pure spastic phenotype and six presenting congenital ataxias. Seventeen mutations occurred in the motor domain of the Kinesin-1A protein, but location of mutation did not correlate with neurological and imaging presentations. When tested in 15 patients, muscle biopsy showed oxidative metabolism alterations (6 cases), impaired respiratory chain complexes II + III activity (3/6) and low CoQ10 levels (6/9). Ubiquinol supplementation (1gr/die) was used in 6 patients with subjective benefit. This study broadened our clinical, genetic, and neuroimaging knowledge of KIF1A-related disorders. Although highly heterogeneous, it seems that manifestations of ataxia-spasticity spectrum disorders seem to occur in most patients. Some patients also present secondary impairment of oxidative metabolism; in this subset, ubiquinol supplementation therapy might be appropriate.

Introduction Both prevalence and clinical features of the various movement disorders in adults with primary mitochondrial diseases are unknown. Methods Based on the database of the “Nation-wide Italian Collaborative Network of Mitochondrial Diseases”, we reviewed the clinical, genetic, neuroimaging and neurophysiological data of adult patients with primary mitochondrial diseases (n = 764) where ataxia, myoclonus or other movement disorders were part of the clinical phenotype. Results Ataxia, myoclonus and movement disorders were present in 105/764 adults (13.7%), with the onset coinciding or preceding the diagnosis of the mitochondrial disease in 49/105 (46.7%). Ataxia and parkinsonism were the most represented, with an overall prevalence at last follow-up of 59.1% and 30.5%, respectively. Hyperkinetic movement disorders were reported in 15.3% at last follow-up, being the less common reported movement disorders. The pathogenic m.8344A > G and POLG variants were always associated with a movement disorder, while LHON variants and mtDNA single deletions were more commonly found in the subjects who did not present a movement disorder. The most common neuroimaging features were cortical and/or cerebellar atrophy, white matter hyperintensities, basal ganglia abnormalities and nigro-striatal degeneration. Almost 70% of patients with parkinsonism responded to dopaminergic therapy, mainly levodopa, and 50% with myoclonus were successfully treated with levetiracetam. Conclusion Movement disorders, mainly ataxia and parkinsonism, are important findings in adult primary mitochondrial diseases. This study underlies the importance of looking for a mitochondrial etiology in the diagnostic flowchart of a movement disorder and may help direct genetic screening in daily practice.

To date, is yet to be elucidated whether the body location of cutaneous melanoma can significantly affect an early dermoscopic diagnosis and, consequently, if it can be regarded as a prognostic factor. To investigate the dermoscopic appearance of early melanomas (EMs) at different body sites; to test the ability of dermoscopists in recognizing specific dermoscopic features in EMs. A pool of 106 experienced dermoscopists evaluated the presence of 10 dermoscopic features assumed as suggestive of malignancy among 268 images of EMs with ambiguous appearance located at 16 body sites. According to 720 evaluations, EMs of the “upper extremities” showed a prevalence of early atypical lentiginous features. EMs of the “anterior trunk” exhibited the lower rate of recognition for all features. EMs of the “rear trunk” can be regarded as an intermediate area, showing high recognition rates of regression-related and chronic-traumatism-related features.

Mitochondrial diseases (MDs) are a large group of genetically determined multisystem disorders, characterized by extreme phenotypic heterogeneity, attributable in part to the dual genomic control (nuclear and mitochondrial DNA) of the mitochondrial proteome. Advances in next-generation sequencing technologies over the past two decades have presented clinicians with a challenge: to select the candidate disease-causing variants among the huge number of data provided. Unfortunately, the clinical tools available to support genetic interpretations still lack specificity and sensitivity. For this reason, the diagnosis of MDs continues to be difficult, with the new “genotype first” approach still failing to diagnose a large group of patients. With the aim of investigating possible relationships between clinical and/or biochemical phenotypes and definitive molecular diagnoses, we performed a retrospective multicenter study of 111 pediatric patients with clinical suspicion of MD. In this cohort, the strongest predictor of a molecular (in particular an mtDNA-related) diagnosis of MD was neuroimaging evidence of basal ganglia (BG) involvement. Regression analysis confirmed that normal BG imaging predicted negative genetic studies for MD. Psychomotor regression was confirmed as an independent predictor of a definitive diagnosis of MD. The findings of this study corroborate previous data supporting a role for neuroimaging in the diagnostic approach to MDs and reinforce the idea that mtDNA sequencing should be considered for first-line testing, at least in specific groups of children.

The term hereditary ataxia (HA) refers to a heterogeneous group of neurological disorders with multiple genetic etiologies and a wide spectrum of ataxia-dominated phenotypes. Massive gene analysis in next-generation sequencing has entered the HA scenario, broadening our genetic and clinical knowledge of these conditions. In this study, we employed a targeted resequencing panel (TRP) in a large and highly heterogeneous cohort of 377 patients with a clinical diagnosis of HA, but no molecular diagnosis on routine genetic tests. We obtained a positive result (genetic diagnosis) in 33.2% of the patients, a rate significantly higher than those reported in similar studies employing TRP (average 19.4%), and in line with those performed using exome sequencing (ES, average 34.6%). Moreover, 15.6% of the patients had an uncertain molecular diagnosis. STUB1, PRKCG, and SPG7 were the most common causative genes. A comparison with published literature data showed that our panel would have identified 97% of the positive cases reported in previous TRP-based studies and 92% of those diagnosed by ES. Proper use of multigene panels, when combined with detailed phenotypic data, seems to be even more efficient than ES in clinical practice.

Movement disorders are increasingly being recognized as a manifestation of childhood-onset mitochondrial diseases (MDs). However, the spectrum and characteristics of these conditions have not been studied in detail in the context of a well-defined cohort of patients. We retrospectively explored a cohort of individuals with childhood-onset MDs querying the Nationwide Italian Collaborative Network of Mitochondrial Diseases database. Using a customized online questionnaire, we attempted to collect data from the subgroup of patients with movement disorders. Complete information was available for 102 patients. Movement disorder was the presenting feature of MD in 45 individuals, with a mean age at onset of 11 years. Ataxia was the most common movement disorder at onset, followed by dystonia, tremor, hypokinetic disorders, chorea, and myoclonus. During the disease course, most patients (67.7%) encountered a worsening of their movement disorder. Basal ganglia involvement, cerebral white matter changes, and cerebellar atrophy were the most commonly associated neuroradiological patterns. Forty-one patients harbored point mutations in the mitochondrial DNA, 10 carried mitochondrial DNA rearrangements, and 41 cases presented mutations in nuclear-DNA-encoded genes, the latter being associated with an earlier onset and a higher impairment in activities of daily living. Among our patients, 32 individuals received pharmacological treatment; clonazepam and oral baclofen were the most commonly used drugs, whereas levodopa and intrathecal baclofen administration were the most effective. A better delineation of the movement disorders phenotypes starting in childhood may improve our diagnostic workup in MDs, fine tuning management, and treatment of affected patients.

Amelanotic/hypomelanotic melanoma (AHM) represents a clinical diagnostic challenge. Dermoscopy improves AHM diagnosis thanks to visualization of little pigment and vascular pattern. Reflectance confocal microscopy (RCM) increases further the diagnostic accuracy of AHM but few and small studies have described in detail RCM features of AHM. We evaluated dermoscopic and RCM features of nine cases of difficult to diagnose hypomelanotic melanomas (HMs) to find clues for their diagnosis. The RCM score was suggestive of melanoma in all cases. The major criteria of nonedged papillae and/or cytological atypia at the dermo-epidermal junction were seen in all cases. Among the minor criteria, roundish pagetoid cells, including hyporeflective pagetoid cells, were found in four out of nine lesions. Dermoscopically, four out of nine HMs did not show prevalent suspicious criteria while revealing suspicious RCM features that were visible only after careful RCM examination by zooming mosaic images. RCM can improve HM diagnostic accuracy but only after extensive evaluation of images. Atypical cells were less reflective and the architectural irregularity was less visible than in pigmented melanoma and zooming was needed to identify both features.

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. Local site reactions, urticaria, and morbilliform eruptions have been recently reported as possible cutaneous adverse reactions after Moderna and Pfizer COVID-19 vaccination1 . We would like to highlight that, in addition to the described skin manifestations related to COVID19 vaccines, AstraZeneca COVID-19 vaccination could trigger a unique skin rash.

Background Leigh syndrome (LS) is a progressive neurodegenerative disorder associated with primary or secondary dysfunction of mitochondrial oxidative phosphorylation and is the most common mitochondrial disease in childhood. Numerous reports on the biochemical and molecular profiles of LS have been published, but there are limited studies on genetically confirmed large series. We reviewed the clinical, imaging, biochemical and molecular data of 122 patients with a diagnosis of LS collected in the Italian Collaborative Network of Mitochondrial Diseases database. Results Clinical picture was characterized by early onset of several neurological signs dominated by central nervous system involvement associated with both supra- and sub-tentorial grey matter at MRI in the majority of cases. Extraneurological organ involvement is less frequent in LS than expected for a mitochondrial disorder. Complex I and IV deficiencies were the most common biochemical diagnoses, mostly associated with mutations in SURF1 or mitochondrial-DNA genes encoding complex I subunits. Our data showed SURF1 as the genotype with the most unfavorable prognosis, differently from other cohorts reported to date. Conclusion We report on a large genetically defined LS cohort, adding new data on phenotype-genotype correlation, prognostic factors and possible suggestions to diagnostic workup.

Background The anatomical location of atypical melanocytic skin lesion (aMSL) was never combined into an algorithm for discriminating early melanomas (EM) from atypical nevi (AN). Aims To investigate the impact of body location on the intuitive diagnosis performed in tele-dermoscopy by dermatologists of different skill levels. A further aim was to evaluate how the integration of the body location could improve an algorithm-aided diagnosis. Methods We retrospectively collected 980 standardized dermoscopic images of aMSL cases (663 AN, 317 EM): data on the anatomical location were collected according to 15 body sites classified into 4 macro-areas of chronically/ frequently/seldom/rarely exposure. Through a teledermatology web platform, 111 variously skilled dermoscopists performed either the intuitive diagnosis and 3 algorithm-assisted diagnostic tests (i.e., iDScore, 7-point checklist, ABCD rule) on each case, for a total of 3330 examinations. Results In the rarely photoexposed area (side, bottom, abdomen), AN were the most tricky (i.e., highest quote of false positives), due to a frequent recognition of dermoscopic features usually considered as suggestive for melanoma in these lesions; the EM at these sites received the highest quote of false negatives, being generally interpreted as "featureless" according to these traditional parameters, that were more frequently displayed on the chronically photoexposed area. In rarely and seldom photoexposed area, intuitive diagnosis fails to achieve adequate accuracy for all aMSLs, as the ABCD rule and the 7-point checklist; by applying the iDScore algorithm the diagnostic performance was increased by 15% in young and 17% in experts. Conclusions The body location of an aMSL can affect the quality of intuitive dermoscopic diagnosis, especially in sun-protected areas. Accuracy can be improved by using the iDScore algorithm that assign a different partial score of each body site.

Background: Lentigo maligna (LM) and lentigo maligna-melanoma (LMM) are histotypes of melanoma arising in skin with cumulative solar radiation damage. The extension of atypical melanocytes to the hair follicle (folliculotropism) is a histopathological feature of LM/LMM. Its role has not been totally clarified, but it may be correlated to treatment response in LM or to progression in LMM. Objective: This retrospective, multicentric study aims to identify dermatoscopic features associated with folliculotropism in LMs/LMMs. Patients and Methods: We analyzed cases of head and neck LMs/LMMs diagnosed between 2005–2014 at Melanoma Units, University of Bologna/Modena/Florence/Siena (Italy), Nice (France): 25 LMs and 73 LMMs were included. Results: Grey circles (44%) indicated an isthmic/bulb level of involvement, which were completely absent in the infundibular LM lesions (P=0.041). In the group of LMMs, light/dark brown pseudonetwork and light brown structureless areas were an indicator of diffuse distribution of malignant melanocytes in the follicular units (P

The “Società Italiana di Dermatologia medica, chirurgica, estetica e delle Malattie Sessualmente Trasmesse (SIDeMaST)” has timely developed an “emergency plan” by issuing a series of informative sheets also named “vademecum” addressed to both dermatologists and patients.

Many aspects of epilepsy in mitochondrial disorders (MDs) need to be further clarified. To this aim, we explored retrospectively a cohort of individuals with MDs querying the “Nationwide Italian Collaborative Network of Mitochondrial Diseases” (NICNMD) database (1467 patients included since 2010 to December 2016). We collected information on age at epilepsy onset, seizure type and frequency, genetic findings, and antiepileptic drugs (AEDs). At the time of our survey, 147/1467 (10%) patients in the NICNMD database had epilepsy. Complete information was available only for 98 patients, 52 males and 46 females, aged 5–92years (mean age 40.4 ± 18.4; 14/98 children/teenagers and 84 adults). Epilepsy was the presenting feature of MD in 46/98 (47%) individuals, with onset at a median age of 19years (range, 0.2–68; < 3years in 14/97 (14%), 3–19years in 36/97 (37%), > 19years in 47/97 (49%)). Moreover, 91/98 patients (93%) displayed multiple seizures, with daily or weekly frequency in 25/91 (28%). Interictal EEG was abnormal in 70/78 (90%) patients, displaying abnormal background (47/70; 67%) and/or interictal paroxysms (53/70; 76%). Eighty of 90 patients (89%) displayed a 50–100% reduction of seizures on AEDs; levetiracetam was the most commonly used. Forty-one patients (42%) carried the m.3243A>G mutation, 16 (16%) the m.8344A>G, and 9 (9%) nuclear DNA (nDNA) mutations. Individuals with early-onset seizures mainly carried nDNA mutations and had a more severe epilepsy phenotype, higher seizure frequency, and disorganized background EEG activity. A better definition of epilepsy in MDs may foster the diagnostic workup, management, and treatment of affected patients, and allow more homogeneous patient stratification.

Background Extensive genetic screening results in the identification of thousands of rare variants that are difficult to interpret. Because of its sheer size, rare variants in the titin gene (TTN) are detected frequently in any individual. Unambiguous interpretation of molecular findings is almost impossible in many patients with myopathies or cardiomyopathies. Objective To refine the current classification framework for TTN-associated skeletal muscle disorders and standardize the interpretation of TTN variants. Methods We used the guidelines issued by the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) to re-analyze TTN genetic findings from our patient cohort. Results We identified in the classification guidelines three rules that are not applicable to titin-related skeletal muscle disorders; six rules that require disease-/gene-specific adjustments and four rules requiring quantitative thresholds for a proper use. In three cases, the rule strength need to be modified. Conclusions We suggest adjustments are made to the guidelines. We provide frequency thresholds to facilitate filtering of candidate causative variants and guidance for the use and interpretation of functional data and co-segregation evidence. We expect that the variant classification framework for TTN-related skeletal muscle disorders will be further improved along with a better understanding of these diseases.

Early and accurate diagnosis of cutaneous squamous cell carcinomas (SCCs) and actinic keratoses (AK) is fundamental to reduce their associated morbidity and to select the correct treatment. Line-field confocal optical coherence tomography (LC-OCT) is a new imaging device that can characterize healthy skin and basal cell carcinoma, but no large studies on keratinocyte cell tumours have yet been published.To identify and describe LC-OCT criteria associated with SCC and AK, and to compare LC-OCT findings in these tumours.A retrospective observational multicentre study was conducted. Lesions were imaged with the LC-OCT device before surgery and examined histologically. LC-OCT criteria for AK/SCC were identified and their presence was evaluated in all study lesions. Univariate and multivariate analyses were performed to compare AK and SCCs, and to investigate differences between in situ and invasive tumours.In total, 158 patients with 50 AK and 108 SCCs (62 in situ and 46 invasive) were included. Cytological and architectural alterations were found in most lesions, and differences were found between AK and SCCs. Although the visualization of the dermoepidermal junction (DEJ) was often hampered by hyperkeratosis and acanthosis, an outlined DEJ without broad strands was observed in almost all AK and almost all in situ SCCs, but in only three invasive SCCs (P 0.001) when the DEJ was detectable.Our results suggest that LC-OCT can help clinicians in the identification of AK and SCC and their differentiation, providing a real-time and noninvasive examination. Further studies are needed to confirm our data.

Though the diagnosis of actinic keratoses is most often clinical, it is sometimes necessary to use non-invasive imaging methods to confirm this diagnosis. Reflectance confocal microscopic examination of actinic keratosis may reveal hyperkeratosis (i.e., detached, isolated or scaly corneocytes), parakeratosis (i.e., nucleated cells in the stratum corneum), dilated vessels and signs of solar elastosis, including clusters of moderately reflecting material and/or undulating shiny elastic fibres that are clearly visible in the superficial dermis. Hopefully, new in vivo microscopic imaging techniques such as line-field confocal optical coherence tomography will make it possible to obtain a three-dimensional examination of the skin and, thus, to further improve diagnostic accuracy of these lesions. © 2019 Elsevier Masson SAS. All rights reserved. Cet article fait partie du numero supplement Keratoses actiniques : comprendre et traiter realise avec le soutien institutionnel de Galderma International.

Born in 1995, teledermatology (TD) turns 25 years old today. Since then, TD evolved according to patients and physicians needs. The present review aimed to summarize all the efforts and experiences carried out in the field of TD and its subspecialties, the evolution and the future perspectives. A literature search was conducted in PubMed and Google Scholar. The state of the art of the "tele-dermo research" included TD and clinical trials, TD/TDS web platforms, TDS and artificial intelligence studies. Finally, the future perspective of TD/TDS in the era of social distancing was discussed. Using TD in specific situations adds several benefits including time-effectiveness of intervention and reduction in the waiting time for the first visit, reduced travel-costs, reduced sanitary costs, equalization of access from patient to specialistic consult. The communication technologies devices currently available can adequately support the growing needs of tele-assistance. A main limit is the current lack of a common clear European regulation for practicing TD, encompassing privacy issues and data management. The pandemic lockdown of 2020 has highlighted the importance of performing TD for all those patient, elderly and/or fragile, where the alternative would be no care at all. Many efforts are needed to develop efficient workflows and TD programs to facilitate the interplay among the different TD actors, along with practice guidelines or position statements.

Wound closure after post-traumatic injuries and/or localized at peculiar body sites (head-and-neck, oral cavity, legs) are particularly challenging and can often be delayed due to local and systemic factors. In case of deep wounds and/or hard-to-heal wounds, grafting of dermal acellular matrices (ADM) is often needed. Though a great variety of synthetic and semisynthetic dermal and skin equivalents are available, viable human dermis, is still considered the most physiological alternative to replace the loss of autologous dermis, by acting as a physiological scaffold that add structural support to soft tissues. To date, human ADMs (hADMs) have been employed in the reconstruction of skin defects affecting almost all body sites, ranging from visceral sites to the skin and subcutaneous tissues. This review aims to investigate the use of hADM at different body sites and their peculiar advantages. A literature search was using the search terms "acellular dermal matrices", "dermal regeneration", "advances wound healing", "human acellular dermal matrices surgery". A total of 50 out of 150 papers was included. Based on the current body if evidence, hADMs appear to bring several advantages, such as: protection of deep structures (e.g. tendons, bones, cartilage and nerves); stimulation of a functional new dermis (rather than a scar); reduction of wound closure time; control of pain and exudate. Finally, hADMs may represent the best treatment option for hard-to-heal wound not only in terms of efficacy and patient satisfaction bout also in terms of sanitary costs, especially across Europe, where hADMs cannot be commercialized as medical devices. This article is protected by copyright. All rights reserved.