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Background: Affecting vascular function, immune regulation, adipocyte and glucose metabolism, adipokines are essential partecipants in the pathogenesis of psoriatic comorbidities such as metabolic syndrome and insulin resistance. Aim of this study was to measure plasma levels of circulating Apelin-36, a newly discovered peptide hormone acting on glucose metabolism and other adipokines in patients with mild to moderate psoriasis and in a control group., Methods: Serum levels of Apelin-36, RBP4, Visfatin, HMW Adiponectin, CRP, fasting glucose and insulin were measured in 19 consecutive patients with mild to moderate psoriasis and 17 healthy subjects., Results: Homeostasis Model Assessment of Insulin Resistance (HOMA IR) Index was significantly increased in patients with psoriasis respect to a control group and positively correlated with BMI (P=0.009). Apelin-36 showed lower levels in the psoriatic population (P=0.016), while the remaining measured adipokines did not show any significant difference between the two groups., Conclusions: In conclusion we confirmed the propensity of psoriatic population to a prediabetic condition even in mild-moderate disease; psoriasis related Apelin-36 lower levels are suggestive of a low-grade inflammatory state. Further studies are needed, to better understand the Apelin related behaviors in different inflammatory settings.

Introduction: Keratinocyte tumors (KT) are frequently observed. Surgery is the treatment gold standard. In some cases, a surgical approach might not be the best option. Radiotherapy (RT) and systemic treatments can frequently cause side effects or be contraindicated. Intralesional methotrexate (MTX) can be a conservative yet effective alternative. We decided to evaluate the effectiveness and safety of intralesional chemotherapy with MTX for the treatment of squamous cell carcinoma (SCC), keratoacanthoma (KA), and basal cell carcinoma (BCC)., Methods: All patients had a histologically confirmed diagnosis of BCC, SCC, or KA and no indication to surgery or RT. MTX was injected subcutaneously proceeding from the periphery of the lesion toward the center. Different protocols in terms of dose, frequency, and length of treatment were used to compare them. Treatment efficacy was evaluated in terms of tumor size reduction. Patients were divided into three groups: responders (improvement of more than 50%), partial responders (< 50%), and non-responders (no improvement or worsening). All data were analyzed using the chi-squared test (χ 2 )., Results: Thirty-five patients were included. Twenty-one patients suffered from SCC, 12 from KA, and 2 from BCC. KA showed a higher response rate than SCC and BCC. For AK, 92% of patients had a complete resolution; 8% were partial responders. For SCC, 47.6% of cases were responders and 14.3% partial responders, while 38% non-responders. All BCCs showed no improvement. A treatment protocol of weekly injections, performed for 4 to 6 weeks, was the most efficient. Doses of 25 mg/ml per session seemed to be most effective. About one third of our patients developed side effects with mild anemia being the most frequent., Conclusions: For selected cases, intralesional MTX can be a safe and effective option for the treatment of KT, especially in case of KA and, to a lesser extent, SCC.

Background: Giant basal cell carcinoma (GBCC) is a basal cell carcinoma (BCC) enlarged in a diameter more than 5 cm. Since GBCCs are a highly infrequent entity and the occurrence rate is approximately 0.5-1% out of all BCC types, only anecdotal cases are reported, and causes and characteristics inducing development of this tumor are not defined., Objectives: Evaluate causative factors and clinico-histological characteristics of GBCCs., Methods: The study is a 6-month, hospital-based case series study performed in 12 Italian dermatologic centers., Results: A total of 59 cases and 458 control BCCs were collected. No significant differences existed between the two groups if we take into account social or cultural factors. The average duration of GBCCs is considerably longer than controls. GBCCs are located on unexposed areas while BCCs are on areas not usually covered by clothes. Superficial histological subtype was more frequent in the BCCs group, while infiltrative in GBCCs. GBCCs showed significantly higher local invasiveness, and greater metastatic capacity. More than half of GBCCs had been previously treated with one or more treatments., Conclusions: Patients with GBCCs appear to belong to two categories: (i) those who present with GBCC due to delay in accessing medical attention, and (ii) those who have BCCs previously treated with inappropriate strategies. Only very few cases can be carried out with intrinsic biological features of tumor aggressiveness. Social and cultural conditions do not appear to be involved in the development of GBCCS. These observations may help clinicians in selecting correct therapeutic strategies in the treatment of BCCs, which give rise to GBCC., (© 2019 The International Society of Dermatology.)

Atopic dermatitis (AD) is an inflammatory disorder of the skin characterized by an impaired immune response and skin barrier function. It is very frequent in adult population being present in up to 10% of population. Quality of life is often reduced in AD patients due to disease burden and symptoms like itch. AD is also frequently associated with psychological diseases such as anxiety or depression. Due to its chronic nature and severity of presentation AD often may not respond to topical treatment and requires systemic treatments which can be associated with significant side effects. A Medline search of the last five years with the keywords "Atopic dermatitis" and "treatment" was performed. Moreover a search throughout the clinicaltrial.gov webpage was performed with the keyword AD. Several topical and systemic treatments are being studied in randomized controlled trials or in case series or in pivotal studies. The progression of the insight on AD pathogenesis have made possible to target single molecules responsible for key aspect of the development of this disease. We discuss the various molecules (small anti-inflammatory molecules, monoclonal antibodies against cytokines) that will be hopefully soon available for the treatment of this disease which still carries an important burden of unmet needs for its treatment.

Background: The main purposes of this study were to evaluate the efficacy of electrochemotherapy in head and neck tumors, to assess local tumor control, its safety profile and its impact on the patients' quality of life., Methods: This is a multicenter prospective, non-randomized phase II trial. This trial was carried out at the Dermatology Clinic of the "Sapienza" University of Rome, at the Dermatology Clinic of the University of Chieti and at the Dermatology Clinic of the University of Turin. Fifty-five patients with head and neck cancer were recruited. Electrochemotherapy was carried out according to the ESOPE guidelines. Statistical analyses were performed using Stata/SE v.12.0 Statistical Software., Results: A significant clinical response was achieved in 50/55 patients with 91% of objective response rate (OR). Thirty-three out of 55 patients showed a complete response (CR) (60%); 17 treated patients had a partial response (PR) (31%). A significantly higher CR rate was obtained in patients not previously treated by surgery (15/19; 79%), with respect to those with a previous excision of the tumor (14/30; 47%) (P=0.025). An additional parameter influencing response is represented by anesthesia: patients treated by ECT with general anesthesia were characterized by significantly higher CR rate (68%) than those treated with local anesthesia (27%) (P=0.014)., Conclusions: Our experience confirmed high efficiency in local tumor control, excellent toxicity profile, tissue preservation with good cosmetic and functional results, even with repeated applications. ECT can represent a first-line treatment in the local management of head and neck cancers.

Background: This was a prospective, multicentre study conducted in 14 Italian psoriasis referral centres (January-June 2014) with the objective of identifying factors associated with different levels of patient awareness on psoriasis., Methods: Overall, 298 patients (119 females, mean age 49.4 years, range 20-88) with a diagnosis of psoriasis (median of 14.1 years) were enrolled. Patients were more knowledgeable about the pathogenic nature of their condition compared with the other parameters (diagnosis, clinical course, prognosis, effect on QoL). Variables associated with significantly higher awareness, included years of education (the higher the educational levels the greater awareness), internet usage, other family member with the disease, diet rich in fruit/vegetables, cigarette smoking and bone and joint involvement., Results: Older age, diabetes, and alcohol abuse were inversely associated., Conclusions: Having established factors that affect awareness in our patients we can now go on to devise educational interventions to address these needs.

Background: Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine member of the tumour necrosis factor (TNF) family. Its role has been investigated in skin cancers and some inflammatory and/or immune-mediated skin diseases. An involvement of TRAIL in psoriasis pathogenesis has recently been hypothesized. We investigated the expression and localization of TRAIL and its receptors in psoriatic skin and measured serum TRAIL. The intracellular pathways activated by TRAIL were assessed to investigate its potential role in the pathogenesis of psoriasis., Methods: Twenty-four consecutive patients with plaque psoriasis and age- and sex-matched healthy subjects were recruited. Serum TRAIL was measured by means of an enzyme-linked immunosorbent assay (ELISA). TRAIL and TRAIL receptors were evaluated by reverse transcription - polymerase chain reaction (RT-PCR) (RNA of lesional and non-lesional psoriatic skin) and by immunohistochemistry (lesional skin). Caspase 8 and NF-kB immunoexpression were also evaluated by immunohistochemistry., Results: RT-PCR demonstrated increased synthesis of TRAIL and its receptors in lesional vs. non-lesional skin. Immunohistochemistry showed a strong staining of TRAIL and TRAIL receptors both in the epidermis and in the dermal infiltrate. Finally, a correlation emerged between caspase 8 and TRAIL immunoexpression in the dermis., Conclusions: Our findings suggest an involvement of TRAIL in psoriasis pathogenesis, probably through an action at the site of the inflammatory infiltrate, likely via caspase 8.

Recent advances in the knowledge of the EGFR pathway have revealed its contribution to distinct immune/inflammatory functions of the epidermis. The purpose of our study was to evaluate the role of EGFR in the regulation of keratinocyte GM-CSF expression. In cultured human keratinocytes, proinflammatory cytokines synergized with TGF-alpha to induce GM-CSF expression. Accordingly, high epidermal levels of EGFR activation are associated with enhanced expression of GM-CSF in lesional skin of patients with psoriasis or allergic contact dermatitis. In cultured keratinocytes, pharmacological inhibition of EGFR activity reduced GM-CSF promoter transactivation, whereas genetic inhibition of AP-1 reduced expression of GM-CSF. Furthermore, EGFR activation enhanced TNF-alpha-induced c-Jun phosphorylation and DNA binding, whereas c-Jun silencing reduced GM-CSF expression. Using two different mouse models, we showed that the lack of a functional EGFR pathway was associated with reduced cytokine-induced phosphorylation of ERK1/2, JNK1/2, c-Jun and reduced keratinocyte-derived GM-CSF expression both in vitro and in vivo. Finally, the analysis of GM-CSF expression in the skin of cancer patients treated with anti EGFR drugs showed an association between ERK activity, c-Jun phosphorylation, and epidermal GM-CSF expression. These data demonstrate that the EGFR pathway is critical for the upregulation of keratinocyte GM-CSF expression under conditions of cytokine stimulation.

Drug-induced lupus is a disease, inducible by several drugs, that shares symptoms and laboratory characteristics with idiopathic lupus erythematosus. We report a case of carbamazepine-induced cutaneous lupus erythematosus which developed after 5 years of treatment in a patient who was on this medication because of an epileptic crisis after cranial trauma. Carbamazepine is a medication rarely implicated in drug-induced cutaneous lupus, moreover there are very few reports of such long periods between the start of therapy and the presentation of the clinical symptoms. We describe this case to emphasize the possibility of cutaneous lupus induction by carbamazepine even after many years of therapy.

Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy characterized by the association of arthritis and psoriasis (Ps). The precise etiology of PsA is unknown, but epidemiological studies supported the existence of a genetic component for the disease. Here we report an association study on a large PsA Italian cohort for DNA variants recently reported as associated alleles at PSORS2 (17q25) in Ps cohorts from the US. We focused on discovering a possible involvement of PSORS2 associated SNPs in pathogenesis of PsA. We selected two SNPs (rs7420, rs734232) within the proximal peak and two SNPs (rs869190 and rs1561946) within distal peak of PSORS2. Our results ruled out PSORS2 alleles as susceptibility factors in arthritis psoriatic patients of Italian origin and suggested that previous linkage signal reported for chromosome 17q25 should be independent on the presence of PsA., (Copyright 2006 S. Karger AG, Basel.)

Cell migration is mediated by a group of chemotactic cytokines called chemokines: low molecular weight molecules that have been shown as important leukocyte chemical attractants to sites of inflammation and infection. Eotaxin-1, also called CCL11, was first described in 1994, as a highly specific eosinophils chemokine. Many cell types including lymphocytes, macrophages, bronchial smooth muscle cells, endothelial cells and eosinophils, are able to produce this chemokine, predominantly after cytokine stimulation, however little is known about its expression in human skin in vivo. Eotaxin-1 also regulates the chemiotaxis and, in some conditions, activation of basophils, mast cells and T lymphocytes. Chemokine receptors are named from their ligand families, thus the CC chemokine eotaxin-1 binds to the CCR3 receptor which is expressed on eosinophis, mast cells, Th2 type lymphocytes and even on keratinocytes. It seems that eotaxin-1 is one of the most important cytokines involved in tissue inflammation playing a central role in the pathogenesis of allergic airway diseases (asthma and rhinitis), in inflammatory bowel disease and gastrointestinal allergic hypersensitivity and recently it has been proposed as a therapeutical target for these conditions. Our group has studied the role of eotaxin-1 in the pathogenesis of two skin conditions: dermatitis herpetiformis and AIDS-associated eosinophilic folliculitis, demonstrating that this chemokine, together with Th2 type cytokines (IL-13 and IL-4) is important in cell recruitment, inflammation and tissue damage; moreover eotaxin has proven to paly an important role in other skin conditions such as, bullous pemphigoid, pemphigoid gestationis, atopic dermatitis and allergic drug reactions Recent advances in the understanding of eotaxin-1-mediated mechanisms of chemotaxis in allergic and inflammatory conditions may predict that therapeutic antagonism is achievable. This paper will focus on the role that eotaxin and its receptor play in the pathogenetical mechanism in a number of dermatologic diseases, some of which, like atopic dermatitis, may benefit from the introduction of novel and more selective therapeutic options.

Dermatomyositis is an inflammatory myopathy characterized by proximal symmetrical muscle weakness with a characteristic cutaneous eruption. Population-based cohort studies provide evidence of an increased frequency of cancer in dermatomyositis patients. Many signs and serology tests have been suggested as markers for malignancy in dermatomyositis. We performed a case-control study on the patients admitted in our institutions for dermatomyositis. Clinical and laboratory data were collected and statistical analysis was performed to reveal important predictive signs of malignancy in dermatomyositis. We found no statistical difference in the clinical or laboratory parameters between the dermatomyositis patients with or without malignancy, with the exception of the erythrocyte sedimentation rate. In our study group an erythrocyte sedimentation rate higher than 35 mm/hr was very strongly associated with the presence or the development of a malignancy. Given the high positive and negative predictive values observed in our study, erythrocyte sedimentation rate evaluation using this cut-off point could be very useful in alerting dermatologists to the need for more in-depth diagnostic procedures in dermatomyositis patients.