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Hidradenitis Suppurativa (HS) is a chronic, Skin Immune-Mediated Inflammatory Disease (sIMID), with a high impact on Quality of Life (QoL). Data on clinical management, comorbidities, psychosocial burden, and psychiatric disorders in paediatric patients with HS is scarce. The aim of our study was to compare clinical characteristics and Patient-Reported Outcome Measures (PROMs) for Health-Related Quality of Life (HRQoL) in adult and paediatric patients with HS. Data were collected on 601 patients with HS, 60 of whom (10.0%) were paediatric. The psychological and HRQoL impact was generally higher in adults than in children, but it was noteworthy also in paediatric patients. Early diagnosis and interventions based on education for the patients and their families and psychological support are the key to optimal disease management and adherence. Our study underlines the need for screening for HS-associated psychiatric disorders and for using age-specific tools to evaluate HRQoL. A multidisciplinary approach involving several specialists is needed, as well as liaison with primary care specialists to improve care, and management of comorbidities and psychological issues in patients with HS.

Abstract Background Non‐photosensitive trichothiodystrophies (TTDs) are a diverse group of genodermatoses within the subset of conditions known as “sulphur‐deficient brittle hair” syndromes. A part of them has only recently been identified, revealing novel causative genes and very rare phenotypes of these genetic skin disorders. At the same time, the molecular basis of previously published and unresolved cases has been revealed through the introduction of innovative genetic techniques. We have previously described the facial phenotype of patients with the Photosensitive form of TTD during childhood. This study marks the beginning of an effort to expand the analysis to include individuals of the same age who do not have photosensitivity. Methods A total of 26 facial portraits of TTD paediatric patients with Non‐photosensitivity from the literature were analysed using computer‐aided technologies, and their facial features were examined through a detailed clinical review. Results Distinct facial features were identified in both Photosensitive and Non‐photosensitive TTDs. Conclusion The present study has comprehensively elucidated the facial features in TTDs, encompassing the Non‐photosensitive clinical spectrum.

Actinic keratosis (AK) is one of the most frequent tumors of the skin; the diagnosis is basically clinical although in some cases it may be difficult to distinguish it from other keratinocytic or even melanocytic neoplasms when it presents in pigmented form. Over the years several clinical classifications and scores to objectify the burden of disease have been created. In this review the most frequent scores and classification systems are summarized along with dermoscopic criteria that allow diagnosis with greater sensitivity and specificity.

Basal cell carcinoma (BCC) is the most common malignant tumour in white populations. Multiple studies demonstrated that the aberrant activation of Hedgehog signaling is a driver of BCC development, and its blockade represents a potential therapeutic target. In Italy, clinicians can prescribe Hedgehog inhibitors (HhIs) Vismodegib and Sonidegib. To highlight the treatment choice of clinicians, we conducted an online survey between November 1 and November 18, 2020 with 33 Italian clinicians from 27 reference hospitals, in which each participant received an anonymous survey consisting of two multiple-choice questions on clinical efficacy and safety profile of Sonidegib and Vismodegib. Respondents reported their opinions on which efficacy and tolerability data of the pivotal phase-II BOLT trial were more relevant in the treatment choice of patients with locally advanced BCC (laBCC). This survey shows that overall response rate (ORR) and the duration of response (DoR) are the most expected across dermatologists and oncologists. The different pharmacokinetic profile of the two HhIs are behind their diverse toxicity spectrum, dose and schedule modification seem to address the choice between vismodegib and sonidegib among dermato-oncology prescribers.

Pemphigus is a life-threatening autoimmune blistering disease affecting skin and mucous membranes. Despite its etiopathogenesis remains largely unknown, several trigger and predisposing factors have been reported. Pemphigus is caused by autoantibodies that target desmoglein 1 and desmoglein 3, impacting desmosome function. However, circulating autoantibodies are often the consequence of a precipitating factor that occurs in predisposed individuals. This review aims to describe and discuss almost all trigger and predisposing factors reported as possible or probable cause of the disease. Among the reported trigger factors that may induce or exacerbate pemphigus, we have found of particular interest: drug intake (especially thiol- and phenol-containing compounds), vaccines, infections, as well as some reports about pregnancy, radiations, emotional stress, pesticides and physical trauma. Moreover, we discuss the possible role of food intake in pemphigus onset and particular attention is given to dietary factors containing thiol, phenol and tannin compounds. A trigger factor is “the straw that breaks the camel’s back,” and often acts together with predisposing factors. Here we discuss how pemphigus onset may be influenced by genetic susceptibility and comorbidities like thyroid diseases, malignancies and other autoimmune disorders.To identify other hitherto unknown trigger and predisposing factors, well designed prospective studies are needed. In this context, future research should explore their connection with the aim to advance our understanding of pemphigus pathogenesis.

Abstract Non-melanoma skin cancer (NMSC) is a tumor that arises from human keratinocytes, showing abnormal control of cell proliferation and aberrant stratification. Cutaneous basal cell carcinoma (cBCC) and cutaneous squamous cell carcinoma (cSCC) are the most common sub-types of NMSC. From a molecular point of view, we are still far from fully understanding the molecular mechanisms behind the onset and progression of NMSC and to unravel targetable vulnerabilities to leverage for their treatment, which is still essentially based on surgery. Under this assumption, it is still not elucidated how the central cellular metabolism, a potential therapeutical target, is involved in NMSC progression. Therefore, our work is based on the characterization of the serine anabolism/catabolism and/or one-carbon metabolism (OCM) role in NMSC pathogenesis. Expression and protein analysis of normal skin and NMSC samples show the alteration of the expression of two enzymes involved in the serine metabolism and OCM, the Serine Hydroxy-Methyl Transferase 2 (SHMT2) and Methylen-ThetraHydroFolate dehydrogenase/cyclohydrolase 2 (MTHFD2). Tissues analysis shows that these two enzymes are mainly expressed in the proliferative areas of cBCC and in the poorly differentiated areas of cSCC, suggesting their role in tumor proliferation maintenance. Moreover, in vitro silencing of SHMT2 and MTHFD2 impairs the proliferation of epidermoid cancer cell line. Taken together these data allow us to link the central cellular metabolism (serine and/or OCM) and NMSC proliferation and progression, offering the opportunity to modulate pharmacologically the involved enzymes activity against this type of human cancer.

BackgroundRecent studies are stressing the idea that the level of Hidradenitis Suppurativa (HS) severity does not always correspond to the same illness load. In fact, it was found that there was no significant association between Skindex-17 and clinical severity of HS, and that some items of the Skindex-17 might be more related to HS severity than others.ObjectiveThe aim of the current study was to explore the associations between different levels of clinical severity of HS (mild, moderate, severe) and the Skindex-17 single-item responses in a large sample of adults patients.MethodsA cross-sectional study with a sample include 547 consecutive HS patients, approaching for the first time the specific dermatologic evaluation. Eligible criteria included age ≥ 18 years, HS diagnosis formulated contextually by the same expert clinician, and providing informed consent. All participants completed the Skindex-17 and were evaluated for the disease clinical severity with the International Hidradenitis Suppurativa Severity Score System. A Network Analysis was conducted, which represents a powerful methodological approach in clinical research. It allows to study specific patterns and the structure of complex system in order to better understand how the elements of the system interact with each-other. Three different Network Analyses were conducted for each group of HS clinical severity by including the items of the Skindex-17 as the nodes of each network.ResultsAmong 547 patients, 40% (219) were female and mean age was of 32.70 (±11.41). Different patterns among items of the Skindex-17 for the three clinical severity groups emerged, meaning that in each group different items are more crucial than others. The psychosocial subscale of the Skindex-17 is the most relevant when assessing the Quality of Life of individuals with different levels of HS severity, however, with the progression of the disease, individuals place attention also on two different aspects of the symptoms subscale of the Skindex-17, irritation and pain, which in turn perfectly reflect the severity of HS, from a clinical perspective.ConclusionThese results provide new insights on the association between levels of HS severity and related Quality of Life, measured with the Skindex-17.

Dermoscopy is widely used for the diagnosis of skin cancers and it increases the accuracy of basal cell carcinoma (BCC) detection. The dermoscopic criteria of BCC have recently been updated and they can be divided into three categories: vascular, pigment-related, and nonvascular/nonpigmentrelated. The objective of our multicentre retrospective study was to report the validity of a new dermoscopic pigment-related feature utilized to detect pigmented BCC (pBCC) (i.e., brown homogeneous blotches (BHB)). Cases of pBCC were collected from the databases of IDI-IRCCS of Rome and from three Italian private dermatology centres. BHB were defined as the presence of circumscribed areas of brown homogeneous pigmentation which are devoid of any dermoscopic specific arrangement (net, fat fingers, etc.) and of other internal dermoscopic structures, except for occasional vascular ones, such as arborizing vessels or globules/dots. Controls included melanocytic and non-melanocytic lesions. We examined images of 270 pigmented lesions (female 145; 51.8%) including 90 histopathological proven pBCC and 180 control cases (i.e., 90 melanocytic and 90 non-melanocytic lesions). BHB were present in 61 cases of 90 pBCC. These results showed a sensibility of 67.8 and a specificity of 93.3 with a positive predictive value of 83.6, negative predictive value of 85.3, posLR 10.2, negLR 0.3; OR 29.4, P value

Autoimmune bullous diseases are a heterogeneous group of rare conditions clinically characterized by the presence of blisters and/or erosions on the skin and on the mucous membranes. Practically, they can be divided into two large groups: the pemphigoid group and the pemphigus group, depending on the depth of the autoimmune process on the skin. Family history of autoimmune disease can often be found, and demonstrating that genetic predisposition is crucial in the development of them. Moreover, numerous environmental risk factors, such as solar radiation, drugs and infections, are known. This study aimed to evaluate how seasonality can affect the trend of BP and PV, especially considering the number of hospitalizations recorded over the course of individual months. The total number of hospitalizations in the twelve months of the year was evaluated. Further, blood chemistry assay and, for some patients, enzyme-linked immunosorbent assay were executed in order to evaluate antibodies. Regarding the severity of the disease BPDAI (Bullous Pemphigoid Area Index) and PDAI (Pemphigus Disease Area Index), score systems were used. Results showed a complex interplay between environmental factors such as seasons and autoimmune conditions.

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Abstract Indoor tanning is associated with an increased risk of skin cancer. Nonetheless, its use is still widespread. We aimed to investigate the socio-demographic and clinical characteristics of sunbed users in a group of participants in the skin cancer prevention campaign organized by the Italian Cancer League (LILT). During almost 2 years, 4409 individuals were screened in 18 centers. Participants reported having used sunbeds before the age of 15 years in 2.2% of cases, while after age 15 the prevalence of use was 22.2%. Participants with complete information were 3692. Sunbed users aged > 15 years were significantly more frequently females, young, living in Northern Italy, highly educated, and current or former smokers. They had darker phototype, more common nevi, had used sunbeds more frequently before the age of 15, reported a history of sunburns, and use of sunscreens. Indoor tanning is an important public health issue and a relevant target for primary prevention. However, not all countries have adopted the recommendations issued by the World Health Organization (WHO) on health risks associated with artificial tanning. A deeper insight into the topic may contribute to identify the best prevention strategies.

Abstract The coronavirus disease (COVID‐19), during its course, may involve several organs, including the skin with a petechial skin rash, urticaria and erythematous rash, or varicella‐like eruption, representing an additional effect of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, as commonly observed in other viral diseases. Considering that symptomatic patients with COVID‐19 generally undergo multidrug treatments, the occurrence of a possible adverse drug reaction presenting with cutaneous manifestations should be contemplated. Pleomorphic skin eruptions occurred in a 59‐year‐old Caucasian woman, affected by a stable form of chronic lymphocytic leukemia, and symptomatic SARS‐CoV‐2 infection, treated with a combination of hydroxychloroquine sulfate, darunavir, ritonavir, sarilumb, omeprazole, ceftriaxone, high‐flow oxygen therapy devices, filgrastim (Zarzio®) as a single injection, and enoxaparin. The patient stopped all treatment but oxygen and enoxaparin were continued and the patient received a high‐dose Desametasone with complete remission of dermatological impairment in 10 days. It is very important to differentially diagnose COVID‐19 disease‐related cutaneous manifestations, where is justified to continue the multidrug antiviral treatment, from those caused by an adverse drug reaction, where it would be necessary to identify the possible culprit drug and to start appropriate antiallergic treatment.

Abstract Non-melanoma skin cancers include basal and squamous cell carcinoma. These tumors have become an important health issue for their high incidence and for the morbidity, especially if untreated for a long period. Over the last 20 years, therapeutic approaches for these tumours have been improved and tailored. In this survey we provided data from one hundred and ten Italian dermatologists regarding knowledge and attitude towards different therapeutic approaches on non-melanoma skin cancers. In our study, we observed that surgery and imiquimod 5% cream were the most used treatment by dermatologists for basal cell carcinoma, while, surgery was the most common treatment for cutaneous squamous cell carcinoma. Furthermore, we observed some differences regarding the prescribed therapies in the different Italian geographical areas (i.e., Mohs’ surgery and electrochemotherapy were more frequently used in Northern compared to Central and Southern Italy whereas immunotherapy was more used in Southern compared to Northern and Central Italy) and even considering the year of specialization of the dermatologists (i.e., immunotherapy with cemiplimab was prescribed mainly by dermatologists with 10–19 years of specialization). However, for locally advanced and metastatic forms of basal and squamous cell carcinoma, Hedgehog Pathway Inhibitors and anti- Programmed cell death protein antibody treatment, respectively, were used in line with the newest evolution of therapies regarding this topic. Considering the importance of skin cancers and its progressive increase in incidence, it is crucial to improve the knowledge of different therapeutic approaches among dermatologists.

BackgroundPemphigus vulgaris is an autoimmune intraepithelial bullous disease involving the skin and the mucous membranes. Imiquimod, a topical therapy for skin basal cell carcinoma, is an amine that induces the production of tumor necrosis factor alfa, interleukin-1 and other cytokines. Pemphigus induced by drugs has been frequently reported, mostly after systemic therapy.Case presentationWe present the case of a 50-year-old man who developed skin, intraoral, and genital mucosae lesions 3 days after a treatment with Imiquimod for multiple superficial basal cell carcinoma of the trunk. Direct and indirect immunofluorescence results were compatible with the diagnosis of pemphigus vulgaris. Enzyme-linked immunosorbent assay was negative for desmoglein 1 and 3, but interestingly, by immunoblotting on keratinocyte extracts a band of 170 kDa was obtained by IgG. The patient, after interrupting Imiquimod application, started a treatment with prednisolone and in 4 weeks showed a complete remission.ConclusionTopical Imiquimod therapy might induce atypical pemphigus vulgaris in some patients.

ObjectivesNon-melanoma skin cancers (NMSC) include two main types: basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC). Generic Health-Related Quality of Life (HRQoL) instruments revealed little to no HRQoL impairment in NMSC patients. Instead, the use of specific skin disease HRQoL tools contradicted those observations. For example, the Skin Cancer Index (SCI) was suggested as a validated instrument for the evaluation of the impact of skin cancers on HRQoL, and has already been validated in several languages, but not in Italian. The aim of this study is to testing some psychometric properties of the Italian version of the SCI questionnaire in a large sample of NMSC patients.MethodsThis is a cross-sectional, single-center, observational study. Firstly, different factor models proposed in the literature were compared and the model with the best fit was identified. Secondly, the psychometric properties of the SCI, convergent validity and reliability, were evaluated.ResultsThe sample was composed of 371 NMSC patients. The factor analysis revealed that a revised version of the original model had the best fit [χ2(df = 85) = 354.53, p

Sarcoidosis is a multisystem disease that affects the skin in 20 to 30% of cases. Skin findings are often the initial presenting signs, and cutaneous sarcoidosis may appear with a wide variety of lesions; it is often considered an imitator of many other skin diseases. Clinical appearance and specific dermoscopic criteria, confirmed by a typical pathology, may guide to the correct diagnosis. We report a case of a man affected by maculo-papular sarcoidosis on the back, in which the detection of cutaneous lesions was the initial step to determine the systemic nature of the disease.

Non-melanoma skin cancers (NMSCs), which include basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and actinic keratosis (AK), are the most common cancer diseases in the Caucasian race. If diagnosed late and improperly treated, BCC and SCC can become locally advanced and metastasize. Malignant melanoma (MM) is less frequent but more lethal than NMSC. Given the individual and social burdens of skin cancers, performing an adequate prevention is needed. Ultraviolet (UV) ray exposure is one of the main risk factors for skin cancer. Thus, the first-choice prevention strategy is represented by photoprotection that can be both topical and systemic. The latter consists of the oral administration of molecules which protect human skin against the damaging effects of UV rays, acting through antioxidant, anti-inflammatory, or immunomodulator mechanisms. Although several compounds are commonly used for photoprotection, only a few molecules have demonstrated their effectiveness in clinical trials and have been included in international guidelines for NMSC prevention (i.e., nicotinamide and retinoids). Moreover, none of them have been demonstrated as able to prevent MM. Clinical and preclinical data regarding the most common compounds used for systemic photoprotection are reported in this review, with a focus on the main mechanisms involved in their photoprotective properties.

Background: Human subcutaneous dirofilariasis caused by Dirofilaria repens is a vector-borne zoonotic disease mostly transmitted from dogs to humans through a mosquito’s blood meal. Heartwarms replication is amplified by the climate change, the increase of the range of suitable vectors, the facilitation of pet travel and the high rate of undiagnosed dirofilariasis in dogs. Observation: We describe a case of a young Romanian woman, resident in Rome for 18 years, that came to our attention for the appearance for five months of a subcutaneous nodule in the left arm. The patient reported that she first felt an insect bite, after which she noticed the onset of an erythematous and itchy wheal in the same skin area, turned into a subcutaneous nodule within a few weeks. The ultrasound examination showed a hypoechoic subcutaneous formation of 1,2 cm in diameter, containing a ribbon-like structure made up of hyperechoic parallel double lines, reminiscent of a warm. Based on this suspicion, we opted for the surgical radicalization of the lesion. The histological examination confirmed the radiological hypothesis of a warm-like foreign body morphologically compatible with Dirofilaria repens. Key message: Our experience shows how a clinical nonspecific skin nodular lesion may conceal an unexpected and unsettling diagnosis of subcutaneous Dirofilaria repens.

Abstract Immunomodulation with anti‐TNF‐α is highly effective in the treatment of various immune‐mediated inflammatory diseases, including hidradenitis suppurativa (HS). However, this may be responsible for unexpected paradoxical psoriasiform reactions. The pathogenic mechanisms underlying the induction of these events are not clear, even though the involvement of innate immune responses driven by plasmacytoid dendritic cells (pDC) has been described. In addition, the genetic predisposition to psoriasis of patients could be determinant. In this study, we investigated the immunological and genetic profiles of three HS patients without psoriasis who developed paradoxical psoriasiform reactions following anti‐TNF‐α therapy with adalimumab. We found that paradoxical psoriasiform skin reactions show immunological features common to the early phases of psoriasis development, characterized by cellular players of innate immunity, such as pDC, neutrophils, mast cells, macrophages, and monocytes. In addition, IFN‐β and IFN‐α2a, two type I IFNs typical of early psoriasis, were highly expressed in paradoxical skin reactions. Concomitantly, other innate immunity molecules, such as the catheledicin LL37 and lymphotoxin (LT)‐α and LT‐β were overproduced. Interestingly, these innate immunity molecules were abundantly expressed by keratinocytes, in addition to the inflammatory infiltrate. In contrast to classical psoriasis, psoriasiform lesions of HS patients showed a reduced number of IFN‐γ and TNF‐α‐releasing T lymphocytes. On the contrary, IL‐22 immunoreactivity was significantly augmented together with the IL‐36γ staining in leukocytes infiltrating the dermis. Finally, we found that all HS patients with paradoxical reactions carried allelic variants in genes predisposing to psoriasis. Among them, SNPs in ERAP1, NFKBIZ, and TNFAIP genes and in the HLA‐C genomic region were found.

Actinic keratosis (AK) is considered a pre-cancerous lesion that may progress into an invasive squamous cell carcinoma. Its prevalence is increasing, and it has been estimated worldwide to range between 1% and 44% of the adult population. The main risk factors for AK are advanced age, fair skin phototype and cumulative sun exposure. Treatment of AK consists of lesion-directed treatment to target single lesions (i.e., cryotherapy, curettage, electrocoagulation, and laser therapy) or field therapy to treat multiple AKs (i.e., photodynamic therapy (PDT), 5- Fluorouracil (5-FU), diclofenac sodium (DIC), imiquimod (IMQ), ingenol mebutate (Ing Meb)). The choice of therapy depends on the number and localization of AKs, patient’s condition, and the patient's tolerability and compliance. In this survey we provided data from one hundred and ten Italian dermatologists regarding knowledge and attitude towards different therapeutic approaches specific for AK. In our study, we observed that the most frequent treatments for AK are cryotherapy and PDT while surgery and laser therapy are the less frequently utilized. The most frequent topical therapies utilized are DIC and IMQ 3.75% cream compared to IMQ 5% cream, Ing Meb, and 5-FU. Choice the correct treatment for AK can be challenging but the adherence to therapy plays a key role to obtain good results. Considering the high and progressive increase in incidence of AK, it is crucial to improve the knowledge of different therapeutic approaches among dermatologists.

Hidradenitis Suppurativa (HS) is a chronic skin disease involving intimate and sensitive areas and affecting physical and mental health. We investigated the prevalence of sexual desire and functioning impairment, and their associations with quality of life, anxiety, depression, minor psychiatric disorders (MPD), and clinical features (e.g., disease severity) in 77 patients with HS who completed self-report measures and answered to questions assessing socio-demographic characteristics, lifestyle habits, and hindered sexuality due to HS. The majority of patients reported hindered sexuality, and poor sexual functioning, while showing good levels of dyadic and solitary sexual desire. No associations were found between clinical severity and sexuality measures. Multivariate analyses showed significant associations of sexual outcome measures with alcohol consumption, low Body Mass Index, family history of HS, and severe skin symptoms. Moreover, we found that the presence of negative psychological factors (i.e., MPD, anxiety, poor mental status) increased the risk of sexual impairment. These findings underline the important role of psychological and sexual aspects in HS patients and suggest that physicians should consider the effect of disease burden on patients' sexual health.

The term non-melanoma skin cancer (NMSC) refers to skin cancer different from melanoma, and it is usually restricted to basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and their pre-cancerous lesions, e.g., actinic keratosis. These conditions represent the most frequent tumors in Caucasians and are characterized by an increasing incidence worldwide and a high socio-economic impact. The term Integrated Care Pathway (ICP) refers to “a complex intervention for the mutual decision making and organization of care processes for a well-defined group of patients during a well-defined period”. The purpose of this paper is to present a proposal from the Italian Association of Hospital Dermatologists (ADOI) for an ICP organization of care of NMSC, considering the hub-and-spoke model in the different geographical areas. This proposal is based on the most recent literature and on documents from the Italian Association of Medical Oncology (AIOM), the European consensus-based interdisciplinary guidelines from the European Association of Dermato- Oncology (EADO), and the National Comprehensive Cancer Network (NCCN). We initially discuss the NMSC outpatient clinic, the role of the multidisciplinary working groups, and the hub-and-spoke model regarding this topic. Then, we define the ICP processes specific for BCC and SCC. The ICP for NMSC is an innovative strategy to guarantee the highest possible quality of health care while the hub-andspoke model is crucial for the organization of different health care structures. Considering the importance on this topic, it is essential to create a valid ICP together with an efficient organization within the different geographical areas.

Cutis laxa (CL) is a group of rare cutaneous disease, inherited or acquired, characterized by inelastic, redundant, wrinkled, loose skin, with loss of elasticity and features of premature aging [...].

The difference between men and women in the impact of keratinocyte carcinomas on quality of life has not been widely studied. This study of 364 patients with keratinocyte carcinoma, measured quality of life using the self-administered 12-item Short Form Health Survey (SF-12) and Skindex-29. Results for both the physical and the mental components of SF-12 were worse in women than in men. For the mental component, women had significantly lower scores compared with men in almost all subgroups, based on demographic and clinical variables. The Skindex-29 emotions mean score was worse in women than in men. Women reported significantly higher level of worry that the disease could get worse and of developing scars, and more depression. On the other hand, men reported lower quality of sleep. The impact of keratinocyte carcinomas on quality of life is generally higher in women than in men. Such data may be important for tailored management of the disease in different categories of patients.

Depression is frequent in patients with hidradenitis suppurativa. However, its relationship with quality of life and clinical severity needs further investigation. In this cross-sectional study, 341 adult, consecutive patients with hidradenitis suppurativa completed the 12-item General Health Questionnaire (GHQ-12), which has been shown to be able to identify cases of major depressive disorder in dermatological patients. The frequency of depression in hidradenitis suppurativa patients was 29.0%. In patients with depression, severity (International Hidradenitis Suppurativa Severity Score System (IHS4)), quality of life (Skindex-17; Dermatology Life Quality Index (DLQI)), and health status (36-item Short Form Health Survey (SF-36)) were significantly worse compared with patients with no depression. The highest linear correlation was observed between GHQ-12 and the psychosocial scale of the Skindex-17 and the SF-36 mental scale. In contrast, correlation between GHQ-12 and clinical severity was poor. Depression is an important comorbidity in hidradenitis suppurativa, which is strongly associated with impairment in quality of life, but not linearly correlated with clinical severity.

Merkel cell carcinoma (MCC) is a rare and extremely aggressive neuroendocrine carcinoma of the skin, with increasing incidence worldwide. This review intends to propose a comprehensive evaluation of MCC epidemiology, clinical features, pathogenetic mechanisms, diagnosis, and therapies. A section is dedicated to immunological aspects and another to the involvement of angiogenesis and angiogenic growth factors in MCC progression, proposing novel diagnostic and therapeutic approaches. Advanced MCC tumors have been treated with immune checkpoint inhibitors with effective results. Therefore, the state of art of this immunotherapy is also examined, reporting on the most recent clinical trials in the field. We conclude by underlining the achievements in the understanding of MCC pathology and indicating the present needs for effective diagnosis and therapeutic management of the disease.

Cutaneous squamous cell carcinoma (cSCC), a non-melanoma skin cancer, is a keratinocyte carcinoma representing one of the most common cancers with an increasing incidence. cSCC could be in situ (e.g., Bowen’s disease) or an invasive form. A significant cSCC risk factor is advanced age, together with cumulative sun exposure, fair skin, prolonged immunosuppression, and previous skin cancer diagnoses. Although most cSCCs can be treated by surgery, a fraction of them recur and metastasize, leading to death. cSCC could arise de novo or be the result of a progression of the actinic keratosis, an in situ carcinoma. The multistage process of cSCC development and progression is characterized by mutations in the genes involved in epidermal homeostasis and by several alterations, such as epigenetic modifications, viral infections, or microenvironmental changes. Thus, cSCC development is a gradual process with several histological- and pathological-defined stages. Dermoscopy and reflectance confocal microscopy enhanced the diagnostic accuracy of cSCC. Surgical excision is the first-line treatment for invasive cSCC. Moreover, radiotherapy may be considered as a primary treatment in patients not candidates for surgery. Extensive studies of cSCC pathogenic mechanisms identified several pharmaceutical targets and allowed the development of new systemic therapies, including immunotherapy with immune checkpoint inhibitors, such as Cemiplimab, and epidermal growth factor receptor inhibitors for metastatic and locally advanced cSCC. Furthermore, the implementation of prevention measures has been useful in patient management.

Background: Systemic photoprotection (i.e., administration of substances such as nicotinamide, carotenoids, and vitamin D) may be important to reduce photocarcinogenesis or to support long-term protection against UV irradiation. Clinical trials showed that oral nicotinamide is effective in reducing the onset of new nonmelanoma skin cancers (NMSCs), while other oral photoprotectors failed to achieve the reduction of new melanoma or NMSC formation in humans. The aim of this study was to summarize the current state of knowledge of systemic photoprotection and to evaluate the knowledge and attitude of dermatologists regarding these treatments. Methods: The survey was conducted on a sample of dermatologists recruited according to a snowball sampling procedure. The questionnaire consisted of a first part asking for characteristics of the participant and a second part with 12 specific questions on their knowledge about systemic photoprotection, particularly their knowledge of astaxanthin, β-carotene, nicotinamide, and vitamin D3. Results: One hundred eight dermatologists answered the survey. Most of them (85.2%) stated that oral photoprotectors have a role in the prevention of skin cancer, and responses mainly mentioned nicotinamide. More than half of them (54.6%) had prescribed all the considered oral photoprotectors, but the majority of them had prescribed nicotinamide, mainly for 2 to 3 months during summer, almost invariably (n = 106) associated with topical photoprotectors. Most dermatologists (>80%) were aware of scientific publications demonstrating an effect of systemic photoprotectors on NMSC. Conclusions: Most Italian dermatologists have positive views on oral photoprotection in skin cancer and are aware of the demonstrated potential of nicotinamide in the prevention of NMSCs.

Basal cell carcinoma (BCC) is the most common human cancer worldwide, and is a subtype of nonmelanoma skin cancer, characterized by a constantly increasing incidence due to an aging population and widespread sun exposure. Although the mortality from BCC is negligible, this tumor can be associated with significant morbidity and cost. This review presents a literature overview of BCC from pathophysiology to novel therapeutic approaches. Several histopathological BCC subtypes with different prognostic values have been described. Dermoscopy and, more recently, reflectance confocal microscopy have largely improved BCC diagnosis. Although surgery is the first-line treatment for localized BCC, other nonsurgical local treatment options are available. BCC pathogenesis depends on the interaction between environmental and genetic characteristics of the patient. Specifically, an aberrant activation of Hedgehog signaling pathway is implicated in its pathogenesis. Notably, Hedgehog signaling inhibitors, such as vismodegib and sonidegib, are successfully used as targeted treatment for advanced or metastatic BCC. Furthermore, the implementation of prevention measures has demonstrated to be useful in the patient management.

Bullous pemphigoid (BP) is the most frequent autoimmune subepidermal blistering disease provoked by autoantibodies directed against two hemidesmosomal proteins: BP180 and BP230. Its pathogenesis depends on the interaction between predisposing factors, such as human leukocyte antigen (HLA) genes, comorbidities, aging, and trigger factors. Several trigger factors, such as drugs, thermal or electrical burns, surgical procedures, trauma, ultraviolet irradiation, radiotherapy, chemical preparations, transplants, and infections may induce or exacerbate BP disease. Identification of predisposing and trigger factors can increase the understanding of BP pathogenesis. Furthermore, an accurate anamnesis focused on the recognition of a possible trigger factor can improve prognosis by promptly removing it.

Pemphigus vulgaris (PV) is an autoimmune blistering disease whose pathogenesis involves both humoral and cell-mediated immune response. Though the pathogenetic role of autoantibodies directed against desmoglein 3 is certain, a number of other factors have been suggested to determine acantholysis in PV. In this study we examined the possible role of CD8+ T cells in the development of acantholysis by a passive transfer of PV autoantibodies using CD8 deficient mice, and we also studied the inflammatory infiltrate of PV skin lesions by immunohistochemical staining. The results of the immunohistochemical staining to study the expression of CD3, CD4, and CD8 in PV skin lesions showed that CD4+ are more expressed than CD8+ in the inflammatory infiltrate of PV lesions, confirming the data of the previous literature. The passive transfer study showed a lower incidence of pemphigus in the group of CD8 deficient mice compared to the control one of wild-type mice. These results suggest that CD8+ T cells may play a role in the pathogenesis of PV, perhaps through the Fas/FasL pathway.