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Background: COronaVIrus Disease 2019 (COVID-19) affects children with less severe symptoms than adults. However, severe COVID-19 paediatric cases are increasingly reported, including patients with Kawasaki disease (KD) or a multisystem inflammatory syndrome (MIS-C) that can present with features resembling KD. Summary: MIS-C is an emerging severe paediatric syndrome associated with COVID-19 that can show overlapping features of KD, KD shock syndrome, and toxic shock syndrome. MIS-C might be an inflammatory disease distinct from KD resulting from an exaggerated immune response. A high prevalence of mucocutaneous manifestations – in addition to gastrointestinal and cardiovascular involvements – was found in MIS-C. The most frequent mucocutaneous findings were conjunctivitis and rash, often described as macular and/or papular or polymorphous. In this article, we present a brief overview of MIS-C with an emphasis on mucocutaneous findings and the relationship with KD.

Hintergrund: Die Symptome der Coronavirus-Infektion 2019 (COronaVIrus Disease 2019, COVID-19) fallen bei Kindern weniger schwer aus als bei Erwachsenen. Allerdings liegen zunehmend Berichte über schwere pädiatrische COVID-19-Fälle vor, darunter Patienten mit Kawasaki-Syndrom (KS) oder einem multisystemischen Entzündungssyndrom (multisystem inflammatory syndrome in children, MIS-C), das KS-ähnliche Merkmale aufweisen kann. Zusammenfassung: MIS-C ist ein neuartiges schweres pädiatrisches Syndrom, das mit COVID-19 in Zusammenhang steht, und bei dem Überschneidungen mit KS, KS-Schocksyndrom und toxischem Schocksyndrom bestehen können. Möglicherweise handelt es sich bei MIS-C um eine entzündliche Erkrankung, die sich vom KS unterscheidet und Folge einer überschießenden Immunreaktion ist. Neben einer gastrointestinalen und kardiovaskulären Beteiligung wurde bei MIS-C auch eine hohe Prävalenz von mukokutanen Manifestationen beobachtet. Die häufigsten mukokutanen Befunde waren Konjunktivitis und Exanthem, das oft als makulös und/oder papulös oder polymorph beschrieben wurde. In der vorliegenden Arbeit geben wir einen kurzen Überblick über MIS-C mit besonderem Augenmerk auf mukokutanen Befunden und dem Zusammenhang mit KS.

Background The therapeutic approaches to patients with chronic spontaneous urticaria (CSU) differ among health care professionals and may be influenced by many factors. Objectives This cross-sectional survey was aimed at evaluating physicians' attitudes regarding therapeutic management of CSU on clinical practice. Methods A study-specific questionnaire was administered to a group of physicians (n=21) with a specialist interest in CSU from different areas of Italy (Group A) and also to other physicians (n=25) who manage CSU only occasionally in their clinical activity (Group B). Results In case of ineffectiveness of second-generation antihistamines at standard doses, higher doses of the same drug were always or frequently prescribed by most physicians in both groups, and 64% in group B and one third in group A usually increased the dose up to twice. Old-generation antihistamines were never used in clinical practice by 14% of survey participants in group A and 24% in group B, with the remaining physicians reporting rare or occasional uses. The prescription of systemic corticosteroids appeared to be more common among physicians in group B. The question concerning the use of alternative drugs in refractory CSU produced different answers between the two groups. Costs and access to specialist reference centers were indicated as the most important barriers to the use of medications different from antihistamines. Conclusions These preliminary results suggest that therapeutic approaches to CSU seem to be heterogeneous in clinical practice and could be at least in part conditioned by the different medical settings where physicians usually work.

Pustular psoriasis (PP) is a clinicopathological entity encompassing different variants, i.e., acute generalized PP (GPP), PP of pregnancy (impetigo herpetiformis), annular (and circinate) PP, infantile/juvenile PP, palmoplantar PP/palmoplantar pustulosis, and acrodermatitis continua of Hallopeau (ACH), which have in common an eruption of superficial sterile pustules on an erythematous base. Unlike psoriasis vulgaris, in which a key role is played by the adaptive immune system and interleukin (IL)-17/IL-23 axis, PP seems to be characterized by an intense inflammatory response resulting from innate immunity hyperactivation, with prominent involvement of the IL-36 axis. Some nosological aspects of PP are still controversial and debated. Moreover, owing to the rarity and heterogeneity of PP forms, data on prognosis and therapeutic management are limited. Recent progresses in the identification of genetic mutations and immunological mechanisms have promoted a better understanding of PP pathogenesis and might have important consequences on diagnostic refinement and treatment. In this narrative review, current findings in the pathogenesis, classification, clinical features, and therapeutic management of PP are briefly discussed.

The coexistence of psoriasis with autoimmune bullous diseases (AIBDs), particularly bullous pemphigoid (BP), has been documented in case reports and series, as well as in epidemiological studies. The onset of psoriasis precedes that of BP in the majority of cases. Patients with concomitant BP and psoriasis are generally younger at the onset of BP and present with fewer erosions and blisters as compared with patients suffering from isolated BP. Intriguingly, it has been speculated that some BP cases with comorbid psoriasis can actually correspond to anti-laminin gamma-1 pemphigoid, a rare form that was recently recognized as a distinct entity and which can mimic BP and/or other subepidermal AIBDs. The pathomechanisms underlying the BP–psoriasis association have not yet been identified, although several hypotheses have been proposed. The most credited among such hypotheses involves the so-called “epitope spreading” phenomenon, with tissue injury secondary to a primary inflammatory process (i.e., psoriasis) leading to the exposure of sequestered antigens evoking a secondary autoimmune disease (i.e., bullous pemphigoid). This narrative review aims to give a brief overview of the association between psoriasis and BP, examining epidemiological, clinical, and immunopathological features, the pathomechanisms underlying this association, the treatments for psoriasis incriminated as potential triggers of BP, and the therapeutic management of patients with psoriasis and BP.

Background: Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease that can affect patients’ quality of life. Dupilumab is the first biologic agent approved for the treatment of patients with inadequately controlled moderate-to-severe AD and its mechanism of action is based on the inhibition of the interleukin (IL)-4 and IL-13 signaling. There are only a few data on the safety of dupilumab in AD patients with comorbidities, including kidney disorders. Materials and Methods: Descriptive retrospective series of three patients with chronic kidney diseases (Alport syndrome, IgA nephropathy, and hypertensive nephrosclerosis, respectively) receiving dupilumab for their concomitant severe AD. Results: Treatment with a standard dosage of dupilumab caused a relevant improvement of AD in all patients without any adverse events or worsening of renal function. In a patient with severe renal failure, the drug was effective and well tolerated without the need for any dose adjustments, also after the initiation of peritoneal dialytic treatment. Conclusion: Our case series suggests the use of dupilumab as an effective and safe treatment for AD patients suffering from renal diseases, although additional studies are required to confirm such preliminary findings.

Omalizumab is a monoclonal anti-IgE antibody which is effective in chronic spontaneous urticaria (CSU), although clinical response appears to be variable in the real-life setting. The aim of this study was to evaluate whether the response of CSU to omalizumab and disease relapse are associated with individual and/or clinical characteristics of patients. We retrospectively evaluated the clinical records of 124 patients treated with omalizumab for moderate to severe CSU refractory to antihistamines. Disease activity was assessed using the urticaria activity score over the last 7 days (UAS7). After 24 weeks of treatment, 91% of patients showed complete remission (UAS7 = 0) or good control (UAS7 7) of CSU. Omalizumab was re-administered in 45 patients because of recurrence of moderate to severe symptoms at week 8 after treatment discontinuation or later, and clinical results achieved with retreatment were similar to those observed in the first course. Among the parameters included in our analysis (age and sex of patients, documented history of atopy or autoimmune thyroid disease, CSU duration and baseline severity, concurrent angioedema, and association with chronic inducible urticaria), none was associated with response to omalizumab in our study population. Similarly, these parameters did not significantly differ between patients who experienced CSU relapse and those without relapse. Predictors of response to omalizumab treatment in CSU patients are still unclear, and further studies are needed to evaluate the presence of baseline factors that can influence treatment outcome.

Introduction: Obesity has been suggested as a risk factor in the progression of malignancies, including melanoma. Most studies defined obesity using body mass index (BMI), although the index is considered an imperfect measure of body composition. Objective: The aim of this article is to examine whether BMI can impact the prognosis of cutaneous melanoma, regardless of anti-tumor therapy. The relationship between BMI and specific prognostic factors in melanoma patients has been reviewed. Methods: Literature search was conducted on PubMed using the terms “melanoma” and “body mass index” or “obesity”. We selected articles, published up to 30 November 2020, examining the prognostic aspects of melanoma. Articles evaluating the risk and incidence of melanoma were excluded as well as studies regarding morbidity and complications following surgical procedures, or those performed in metastatic melanoma patients treated with anti-tumor therapies. Results: Mixed results have emerged from studies assessing the clinical outcomes in melanoma patients in relation to BMI. More consistent data seem to support the relationship between BMI and Breslow thickness. Conclusions: Studies that focus specifically on the link between obesity and melanoma prognosis are limited; further research is needed to deepen our knowledge on this link.

Irisin is an adipo-myokine, mainly synthetized in skeletal muscles and adipose tissues, that is involved in multiple processes. Only a few studies have evaluated serum irisin in psoriatic patients. This study aims to analyze serum irisin levels in patients with chronic plaque psoriasis, to compare them with values in controls, and to assess whether concentration of circulating irisin correlates with the severity of psoriasis, calculated by means of Psoriasis Area and Severity Index (PASI). We enrolled 46 patients with chronic plaque psoriasis; the control group included 46 sex- and age-matched subjects without any skin or systemic diseases. Serum irisin levels were measured by competitive enzyme linked immunosorbent assay. Our results showed a non-significant increase in serum irisin concentration in psoriatic patients compared to controls. A negative non-linear correlation between PASI and irisin levels was detected in psoriatic patients. Indeed, dividing patients according to psoriasis severity, the negative association between irisin and PASI was stronger in patients with mild psoriasis than in patients with higher PASI scores. Several control variables we tested showed no significant impact on serum irisin. However, erythrocyte sedimentation rate in the normal range was associated with significantly higher irisin levels in psoriatic patients. In conclusion, although irisin levels were not significantly different between controls and psoriatic patients, irisin was found to be negatively associated with psoriasis severity, especially in subjects with low PASI scores; however, further studies are needed to clarify the role of irisin in subjects with psoriasis.

The link between anthropometric indices, including height, and cancer risk and/or progression has attracted considerable interest in recent years. Adult height results from the complex interplay between genetic, hormonal, nutritional, and other environmental factors and has been found to contribute to the risk of several selected malignancies, although it has not been implicated as a real cause per se. A number of studies have investigated the height-melanoma relationship, showing controversial results so far. In this review, we summarize the epidemiological data regarding the association between height and melanoma risk and analyze the potential underlying mechanisms.

Background Emerging data have strengthened the importance of substance P (SP) as a proinflammatory mediator in human pathology. A role for SP in the pathogenesis of urticaria has long been hypothesized. Methods Literature data regarding the possible role of SP in chronic urticaria/chronic spontaneous urticaria (CSU) have been reviewed and summarized in this manuscript. This review is based on pertinent articles that were retrieved by a selective literature search in the PubMed database. Articles in English published up to July 2018 were taken into consideration. Results Recent studies in patients with CSU have demonstrated that circulating levels of SP are significantly elevated, in correlation with disease severity, and that SP-positive basophils are upregulated. SP has been shown to trigger degranulation in basophils derived from CSU patients. Moreover, SP can be involved in pseudoallergic reactions and may act as a histamine-releasing factor in a subset of patients with CSU. Current evidence suggests that the biological activity of SP can be exerted not only through the conventional NK-1 receptor but also through the recently identified Mas-related G protein-coupled receptors. MRGPRX2 can cause mast cell activation and has been found to be upregulated in the skin of patients with severe chronic urticaria. Conclusions Many findings seem to support the pathogenic involvement of SP in chronic urticaria/CSU. However, further studies are necessary to elucidate the role of SP as a mediator in CSU pathogenesis and a potential new therapeutic target.

BACKGROUND Chronic spontaneous urticaria (CSU) is a heterogeneous condition whose management can be complex and challenging. The 0bjectives is to evaluate physicians' attitudes regarding practical aspects of CSU management, including adherence to international guidelines, criteria and instruments for CSU assessment, prescription of laboratory investigations and role of dietary measures. METHODS A cross-sectional survey was conducted using a study-specific questionnaire. It was administered to a group of physicians with a specialist interest in CSU from different areas of Italy definable as "CSU experts" (Group A; n=21) and subsequently to other physicians who managed CSU only occasionally in their clinical activity (Group B; n=25). RESULTS The EAACI/GA²LEN/EDF/WAO guidelines were considered very or moderately useful by the majority of participants. Significantly more physicians in group A reported that such guidelines were always followed in clinical practice (P=0.0008). Instruments for the assessment of CSU severity/activity and quality of life were used in clinical practice significantly more often by CSU experts as compared to group B. Dietary measures were frequently suggested for CSU patients by nearly three quarters of group B members and by only 5% of CSU experts (P

Tea tree oil is an essential oil obtained by distillation from the leaves and terminal branchlets of Melaleuca alternifolia and is now present in numerous products for body care and self-medication. We report a case of allergic contact dermatitis to tea tree oil in a young man who was applying a lotion containing tea tree oil on a wart localized on the plantar aspect of the right big toe, which had previously been treated with cryotherapy. He developed a severe eczematous eruption on the right foot and the right leg, with subsequent id reactions affecting the right thigh, the contralateral lower limb, the trunk and the upper limbs. The lotion was discontinued, and the dermatitis resolved after topical corticosteroid therapy. Patch testing with the aforementioned lotion 10% pet. and oxidized tea tree oil 5% pet. identified tea tree oil as the culprit agent of the dermatitis. This case report confirms that products made of natural ingredients, often perceived to be harmless, can cause allergic reactions.

Background The infection caused by the recently identified SARS-CoV-2, called coronavirus disease-19 (COVID-19), has rapidly spread throughout the world. With the exponential increase of patients worldwide, the clinical spectrum of COVID-19 is being better defined and new symptoms are emerging. Numerous reports are documenting the occurrence of different cutaneous manifestations in patients with COVID-19. Objectives To provide a brief overview of cutaneous lesions associated with COVID-19. Methods A literature search was performed in the PubMed, Scopus and Web of Science databases up to 30 April 2020. This narrative review summarizes the available data regarding the clinical and histological features of COVID-19-associated skin manifestations. Results The literature reports showed a great heterogeneity in COVID-19-associated cutaneous manifestations, as well as in their latency periods and associated extracutaneous symptoms. Pathogenic mechanisms are unknown, although the roles of a hyperactive immune response, complement activation and microvascular injury have been hypothesized. Based on our experience and the literature data, we subdivided the reported cutaneous lesions into six main clinical patterns: (i) urticarial rash; (ii) confluent erythematous-maculopapular-morbilliform rash; (iii) papulovesicular exanthem; (iv) chilblain-like acral pattern; (v) livedo reticularis-livedo racemosa-like pattern; and (vi) purpuric 'vasculitic' pattern. These six patterns can be merged into two main groups: the first - inflammatory and exanthematous - includes the first three groups listed above, and the second includes the vasculopathic and vasculitic lesions of the last three groups. Conclusions The possible presence of cutaneous findings leading to suspect COVID-19 puts dermatologists in a relevant position. Further studies are needed to delineate the diagnostic and prognostic values of such cutaneous manifestations.

Methotrexate (MTX) is one of the mainstays of treatment for several immune-mediated inflammatory joint and skin diseases, especially rheumatoid arthritis (RA) and moderate-to-severe psoriasis. Oral MTX has been used for the treatment of such diseases for decades for many reasons. There is, however, a relevant interpatient variability of clinical and safety outcomes that can also be related to differences in patients' individual pharmacogenomic profile. Orally administered MTX has been found to have a saturable intestinal absorption and nonlinear pharmacokinetics, with significant consequences on drug bioavailability and clinical efficacy. The current evidence shows that parenterally administered MTX results in rapid and complete absorption, higher serum levels, and less variable exposure than oral dosing. The use of parenteral MTX, particularly when administered as a subcutaneous (SC) injection, has recently raised great interest in order to overcome the limitations of oral MTX. The effectiveness and safety of SC MTX have mostly been assessed in rheumatological settings, especially in patients with RA. There are only a limited number of data on SC MTX in juvenile idiopathic arthritis and even fewer in psoriatic disease. Various clinical experiences have suggested that SC MTX is more effective than oral MTX and may provide significant benefit even in patients in whom oral MTX proved to be inadequate. The increased efficacy of SC MTX resulting from higher drug exposure compared with oral MTX has been associated with a similar safety profile and in various reports even with a lower frequency of gastrointestinal complaints. The aim of this article was to review the available literature data on SC MTX treatment of inflammatory arthritis, with special emphasis on RA and psoriasis, examining differences with oral MTX treatment. A brief mention of pharmacokinetics, pharmacodynamic features and pharmacoeconomic considerations is also given.

We evaluated the prescription appropriateness of cyproterone acetate in combination with ethinylestradiol (CPA/EE) in a primary care setting before and after the 2013 European Medicines Agency’s (EMA) recommendation relating to the risk profile of CPA/EE. Data were obtained from the Health Search IMS Health Longitudinal Patient Database (HSD). We compared the results from 2011 to 2012 with the results of 2014, namely before and after the 2013 EMA recommendation, and investigated the burden of concurrent use of CPA/EE and other hormonal contraceptives (HCs) and the reported indication at the time of CPA/EE prescription. Overall, 1189 new users of CPA/EE were identified: 495 in 2011, 446 in 2012, and 261 in 2014. Concomitant use of CPA/EE and other HCs was found in 1% of cases in 2011–2012 and 2% of cases in 2014, while potential concomitant use was observed in 4% of cases in 2011 and 2% of cases in 2012 and 2014. A recent (within 365 days) diagnosis of any hyperandrogenic condition was detected in 22 and 24% of CPA/EE users in 2011 and 2012, respectively, and in 24% of cases in 2014. The percentage of CPA/EE users with a recent acne diagnosis and/or treatment was 19, 21, and 18% in 2011, 2012, and 2014, respectively. Apart from an overall reduction in CPA/EE prescriptions in the HSD, no substantial difference was found in terms of the proportions of patients diagnosed with acne or other hyperandrogenic conditions and/or potential concomitant use of HCs before and after the EMA recommendation.

SummaryBackground Chronic spontaneous urticaria (CSU) is a common skin disease, but there is a paucity of precise epidemiological data on this disease. Objectives To obtain information on the epidemiology of CSU in Italy. Methods The data source was the Health Search IMS Health Longitudinal Patient Database. The study population was formed by patients aged ≥ 15 years, registered with a total of 700 general practitioners, homogeneously distributed across Italy. An algorithm based on the International Classification of Diseases, ninth revision, Clinical Modification was used for the identification of patients with CSU. The annual prevalence and incidence rates of CSU over a 12-year period (2002–2013) were estimated, along with demographic and clinical determinants. Results The annual prevalence of CSU ranged from 0·02% in 2002 to 0·38% in 2013. The incidence was 0·10–1·50 per 1000 person-years. For both prevalence and incidence rates, female patients outnumbered male. The risk of CSU was statistically significantly higher in the presence of the following variables: obesity; anxiety, dissociative and somatoform disorders; malignancies; use of immunosuppressive drugs; and chronic use of systemic corticosteroids. History of autoimmune thyroiditis showed a trend towards an increased risk of CSU, though it was not statistically significant. Smoking was associated with a significantly reduced risk of CSU. Conclusions Our findings on CSU prevalence are consistent with those obtained in previous studies. Furthermore, this large population-based study provides important information regarding the association of CSU with demographic and clinical determinants, which have been examined in the primary-care setting.

The potential carcinogenic risk of antihypertensive drugs has been examined in several studies that reported controversial results. The association between treatment with antihypertensives and risk of skin cancer has also been questioned, considering the long-term administration of such drugs and the ability of some agents to cause photosensitive reactions. In fact, experimental and epidemiologic findings suggest a link between drug-induced photosensitivity and skin cancer, possibly through the induction of DNA damage in predisposed individuals. Antihypertensive medications might influence skin homeostasis through additional mechanisms. For instance, some antihypertensive drugs can affect epidermal differentiation by interfering with calcium or sodium channels in the skin. Mediators in the renin-angiotensin system (RAS) are also involved in the modulation of cellular proliferation and angiogenesis. Of note, the existence of RAS has been recognized in many organs and tissues, including the skin. The available data regarding the relationship between use of different types of antihypertensives and skin cancer risk do not allow to draw definite conclusions at present. The aim of this article is to summarize the current evidence about the association of antihypertensive use with risk of non-melanoma skin cancer, melanoma, lip cancer and cutaneous lymphoma. A brief mention of the role of beta-blockers in melanoma progression has also been added.

Actinic cheilitis (AC) is a common premalignant condition that requires an effective treatment to reduce the risk of malignant transformation. Photodynamic therapy (PDT) has been recently added to the armamentarium available for AC treatment. Daylight PDT (D-PDT) is a novel PDT modality in which the activation of the topical photosensitizer is induced by the exposure to natural daylight instead of artificial light sources without preliminary occlusion. This simplified procedure was found to be more tolerated as compared to conventional PDT. We report our preliminary experience on the use of D-PDT using methyl-aminolevulinate cream in 10 patients with refractory AC of the lower lip. Patients received two consecutive D-PDT sessions with an interval of 7-14 days. At 3 months after therapy, a complete response was observed in seven patients, with sustained results in five patients over an observational period of 6-12 months. Treatment was well tolerated.

The guidelines for the management of urticaria in adults and children have been revised and updated recently. However, there are few data in the literature concerning several aspects of this disease in the elderly (e.g., epidemiology, etiopathogenesis, clinical aspects, association with co-morbidities, efficacy and safety profiles of treatments, and management strategies). This is an obvious deficiency in the data, as this disease causes a deterioration in quality of life, affecting the quality of sleep, everyday life habits and activities, and inducing severe disability. Chronic spontaneous urticaria (CSU) can also be associated with internal, infectious, autoimmune, or neoplastic diseases. It is therefore necessary to pay particular attention to these clinical issues through appropriate clinical examinations. At the same time, the specific features of medications used to treat CSU in the elderly should be carefully evaluated, as its pharmacological treatment raises a number of problems related both to the clinical condition of the patient and to concomitant diseases, as well as to the polypharmacotherapy, which is common in older subjects and may cause safety problems because of the drug interactions. Non-sedating new-generation antihistamines are the mainstay treatment of CSU for the elderly. The efficacy and safety of alternative treatment options have not been assessed in the geriatric population with CSU; corticosteroids and cyclosporine (ciclosporin) should be used by this population with extreme caution. Similarly, there are no data regarding the actual safety profile of the new-generation antihistamines at higher doses than those recommended in elderly patients.

Postmarketing Phase IV Treatment adherence to anti-tumor necrosis factor alpha (anti-TNF-α) agents is marker of treatment success, but overall efficacy of anti-TNF-α therapy decreases over time leading to a progressive loss of adherence. The present observational study was conducted in order to estimate the long-term adherence to etanercept in patients affected by plaque-type psoriasis, evaluating differences among intermittent and continuous treatment regimen. Our findings reflect routine clinical practice in three academic referral centers and show high treatment adherence with etanercept in psoriatic patients. Treatment survival was consistently high in the short/medium term. The univariate analysis showed longer treatment duration in patients undergoing intermittent treatment regimen (mean 1,706 days) compared with continuous regimen (mean 1,249 days). Results showed that a flexible pulsed treatment with etanercept can be optimal in terms of clinical success and adherence.

The international EAACI/GALEN/EDF/WAO guideline suggests a stepwise approach for the therapeutic management of chronic spontaneous urticaria (CSU), outlined in an algorithm. The aim of this article is to summarize and review the evidence available on alternative treatment options for CSU outside of this algorithm.Although CSU is a common disease, there are a limited number of high-quality studies, and only antihistamines and omalizumab are licensed for its treatment. Most studies regarding alternative therapies for CSU show methodological limitations and a high risk of bias. For many therapies, only case reports and uncontrolled studies exist. Recent publications on alternative treatments for chronic urticaria/CSU include reports on the use of adalimumab, rituximab, vitamin D, probiotics, histaglobulin, injection of autologous whole blood or serum, and phototherapy.Numerous treatments beyond the guideline algorithm have been evaluated in patients with refractory CSU. The global level of evidence to support their efficacy in CSU is low or very low. Further research is needed to assess the efficacy and safety of alternative therapies of CSU to manage adequately those patients who do not respond to the treatments included in the algorithm.

The sudden eruption of melanocytic nevi has been associated with a number of conditions, such as bullous skin diseases, immunodeficiency and immunosuppression. The exact mechanisms leading to the development of eruptive melanocytic nevi are unknown. Areas covered: The aim of this article is to review the literature concerning eruptive melanocytic nevi following the administration of immunosuppressive drugs and other medications. Expert opinion: The literature regarding the development of eruptive nevi in association with pharmacological therapies includes a relatively low number of reports. Prevalence of this phenomenon is likely to be underestimated, thus reporting should be encouraged in order to better define the actual significance and related clinical implications. The development of multiple melanocytic nevi during immunosuppressive treatments highlights the importance of immune system integrity in the regulation of nevi growth. The observation of eruptive nevi as an unexpected effect of targeted therapies for specific types of cancer, including melanoma, provided intriguing hints to understand the mechanisms underlying this paradoxical event. The synergistic role of additional triggers in the occurrence of drug-induced eruptive nevi has not been explored and may be an interesting area of research.

Background Only a few studies have assessed treatment usage in clinical practice among patients with chronic spontaneous urticaria (CSU). Methods The aim of this study was to evaluate patterns of medications used for CSU, analyzing the electronic patient records contained in the Italian general practice Health Search IMS Health Longitudinal Patient Database (HSD). The study period was from January 2002 to December 2013. Results The most frequent prescriptions during the year following CSU diagnosis were H1-antihistamines (78.47%) and corticosteroids (49.20%). Different medications were given to a limited number of CSU patients. Conclusions The results of our study have shown that H1-antihistamines were the most prescribed drugs to treat CSU, reflecting their role as the mainstay of CSU treatment. Systemic corticosteroids continue to be frequently prescribed for CSU in clinical practice. Alternative drugs were used only in very few patients, suggesting the possibility that severe refractory cases of CSU are undertreated in clinical practice.

Chronic spontaneous urticaria (CSU) is a disabling condition that causes deterioration of quality of life.The international EAACI/GA(2)LEN/EDF/WAO guidelines have provided a stepwise treatment algorithm for CSU management. Second-generation H1-antihistamines are the first-line treatment, and the second step is the up-dosing of the same drugs. In refractory patients, the guidelines recommend the addition of omalizumab, ciclosporin A or montelukast. Systemic corticosteroids can be used as a short course during acute exacerbations. A plethora of alternative treatments has been evaluated, although the overall level of evidence for such treatments is low. Future treatment options may include inhibitors of skin mast cells and antagonists to mast cell-activating signals that are relevant for the induction of CSU signs and symptoms.The only licensed options included in the guidelines algorithm are standard-dosed second-generation H1-antihistamines and omalizumab. High-quality evidence has documented a rapid and strong symptomatic effect of omalizumab in CSU, although the optimal long-term regimens should be further investigated. The role of alternative drugs deserves additional studies. The potential of the existing treatments for inducing remission of CSU is unknown, and this is an important area of research, as is the evaluation of predictors of response, prognostic factors, and pathomechanisms.

This mono-center randomized, controlled, double-blind study evaluates the safety and efficacy of MD2011001 cream versus placebo, in mild-to-moderate atopic dermatitis (AD). MD2011001 is a nonsteroidal topical cream containing vitamin E, epigallocatechin gallate and grape seed procyanidins.Patients with AD (corresponding to an IGA score of 2 or 3), involving the face, the perioral/periocular area and/or the neck, were enrolled. Patients were randomized 1:1 ratio to receive MD2011001 or placebo before the start of the study (D0), then evaluated after 7 days, and after 28 days. The study was approved by the Local Independent Ethics Committee and conducted according to the Declaration of Helsinki and local regulations. The statistical tests used were the Wilcoxon test and the Mann-Whitney U-test.Forty-four patients (29F and 15M) were enrolled. The IGA values showed a statistically significant reduction during the treatment period obtaining a favorable safety profile and local tolerance for both the products. The reduction in the surface area affected by AD was significantly faster with MD2011001.This study focuses on very sensitive areas known to be particularly susceptible to local complications.These results suggest the usefulness of an emollient treatment for mild/moderate AD.

Combination of systemic biological and traditional agents is increasingly used for the treatment of “high-need” patients with psoriasis. There are only limited data on the combination of cyclosporine (CsA) with biologicals. We report our experience concerning the use of etanercept in combination with CsA, given at a dose of 3–5mg/kg two days per week, in patients with insufficient response of psoriasisto etanercept monotherapy. The retrospective analysis of 17 patients showed that the addition of CsA for 2–8 months was capable of inducing a relevant clinical benefit in a total of 12 patients. The combination treatment was tolerated by all patients except one who had to stop CsA treatment because of repeated hypertensive crises.

Alcohol has long been suspected to be a triggering and precipitating factor of psoriasis. Alcohol misuse is common in patients with moderate-to-severe psoriasis and appears to impair treatment outcome.In this article, the authors review the available data regarding the metabolic and toxicological interactions between anti-psoriasis systemic drugs and ethanol and/or alcoholic beverages. Special attention is given to the influence of alcohol consumption on the hepatotoxic risk of some anti-psoriasis drugs. The article was prepared using a MEDLINE literature search.The available knowledge highlights the existence of a few significant pharmacological interactions, such as the reduced exposure to cyclosporine by red wine, the possible increase of cyclosporine levels following a heavy acute alcohol intake, and, especially, the conversion of acitretin to etretinate, in the presence of ethanol, with important implications in females of child-bearing potential. There are limited data on the contributing role of alcohol in the hepatotoxicity induced by some anti-psoriasis drugs and the existing information on this topic is still controversial. However, further investigation is needed to assess the relevance of interactions between alcohol consumption and drug therapy for psoriasis, under both pharmacological and toxicological perspectives. Long-term prospective studies on large cohorts of patients are warranted to disclose the actual significance of such potential interactions in clinical practice.

Background: Platelets are implicated in many pathophysiological processes, including inflammation and immunity. Ever-growing evidence suggests the active involvement of platelets in the pathogenesis of various inflammatory disorders, including cutaneous inflammatory diseases. A limited number of studies have investigated the role of platelets in chronic urticaria (CU). In this review, we summarize the current knowledge regarding the role of platelets in chronic spontaneous and inducible urticarias. Methods: A literature search was performed using PubMed and Google Scholar, and the references of relevant literature were reviewed. Results: Overall, in CU patients, conflicting results have been obtained from the assessment of platelet indices, such as mean platelet volume, platelet count and distribution width, as well as markers of platelet aggregation and activation. Nevertheless, a few studies showed significant changes of such parameters in CU patients compared to controls, in apparent correlation with clinical severity, autoreactivity and/or inflammatory status. Conclusions: In the absence of definitive conclusions, the pathogenic role of platelets in CU needs to be further explored. Platelets might represent a link between inflammation, coagulation and histamine release in the pathophysiological network of CU.

Over the last years, data have been accumulating regarding a possible association between alcohol and psoriasis. While it is still unclear whether alcohol misuse represents a true risk factor or merely an epiphenomenon of the cutaneous disease, a number of studies support the role of ethanol and its metabolites as triggering factors of psoriasis. A drinking habit also appears to exacerbate a preexisting psoriasis, and the magnitude of alcohol consumption may be related to both a higher incidence and severity of psoriasis. Evidence also shows that deaths from alcohol-related causes are significantly more frequent in patients with psoriasis than in normal controls. Alcohol consumption may adversely affect psoriasis through multiple mechanisms, such as increased susceptibility to infections, stimulation of lymphocyte and keratinocyte proliferation, and production of proinflammatory cytokines. Moreover, alcohol misuse can predispose to a greater risk of liver disease and potential drug interactions. Alcoholic and non-alcoholic liver diseases have both been found to be common in psoriatic patients. Tumor necrosis factor (TNF)-alpha, a key cytokine in psoriasis pathogenesis, has been found to have a crucial role in alcoholic hepatitis, and small preliminary studies have evaluated the effect of anti-TNF therapy in this condition. However, the use of anti-TNF-α drugs in alcoholic hepatitis is still controversial and needs to be further investigated. In this review, the relationship between alcohol and psoriasis will be reviewed and discussed, taking also into account recent findings related to liver disease and therapeutic implications.

Background The last decades have witnessed an increasing interest for the psychosocial aspects of chronic skin diseases, such as psoriasis. Nonetheless, systematic assessments of the impact of psoriasis on patients’ lives are rarely done in daily clinical practice. The existing instruments are mostly meant to be completed by patients alone, and rarely comprise a graphical representation of the results. Objective To develop a questionnaire allowing both a quick assessment of the impact of psoriasis on patients and, at the same time, an intuitive graphic visualization of the outcome of the test. Methods A preliminary version of an Italian questionnaire aimed to assess the global impact of psoriasis on patients, meant to be filled in together by the patient and the dermatologist and to produce visual, intuitive results, was developed through focus groups. The instrument was then the object of a Delphi survey addressed to a panel of experts, to assess both the need of possible improvements of the questionnaire (in terms of the formulations of the questions and of the domains to be explored) and the usefulness of the questionnaire. Results A 10-item questionnaire in Italian, taking into account different aspects of the burden of psoriasis on the patient, was developed. The answers are given on a 10-point visual analogue scale and graphically represented on a disc as a polygon. Conclusions A formal validation of the questionnaire and a study to assess potential clinical and psychological benefits of a systematic implementation of the instrument in daily practice are planned.

Cyclosporine A (CsA) effectively controls psoriasis, however, its long-term continuous use is not recommended. This study aims to evaluate the efficacy and tolerability of week-end CsA microemulsion for the reduction of relapse rate in patients with chronic plaque psoriasis who had achieved clinical remission following continuous CsA therapy. The PREWENT (Psoriasis Relapse Evaluation with Week-End Neoral Treatment) study was a 24-week, randomized, double-blind, multicenter study, carried out in 22 Italian hospital or university Dermatology units. CsA was discontinued for 8 days previous to the patients being randomized to oral CsA 5 mg/kg/day or placebo for two consecutive days/week, for a total period of 24 weeks. The primary endpoint was clinical success rate at week 24, defined as the proportion of patients with no clinical worsening (no relapse or a Psoriasis Area and Severity Index [PASI]

Biological drugs targeting tumor necrosis factor-α, such as infliximab, are highly effective in psoriasis. The interference with keratinocyte apoptosis has been included among the possible effects of infliximab in psoriasis, although the available data are still controversial. The purpose of our study was to verify the action of infliximab on psoriatic keratinocytes. Keratinocyte apoptosis was evaluated in the lesional psoriatic skin of 11 patients at baseline and a different time point during treatment with infliximab. Infliximab (5 mg/kg) was given intravenously at weeks 0, 2, and 6, followed by maintenance infusions every 8 weeks. Pretreatment with intravenous hydrocortisone was performed prior to each infusion. Keratinocytes with apoptotic features were histologically identified according to the following changes: chromatin condensation at the periphery of the nucleus, cytoplasmic vesiculation, nuclear fragmentation, nuclear pyknosis. Immunohistochemical assessment of p53 and caspase-3 expression was also performed. At baseline, prior to treatment with infliximab, lesional epidermis showed 1.2-3.2% p53-positive apoptotic keratinocytes in the basal zone. The number of p53-positive apoptotic keratinocytes increased after treatment with infliximab, already at day 1-2 after the first infusion, and such cells were localized at basal and suprabasal layers or were through all layers. There was no immunoreactivity for caspase-3 at any time point examined. Our results suggest that induction of p53-related keratinocyte apoptosis might be one of the mechanisms of infliximab action in psoriasis.

Current epidemiological data support the association between psoriasis and cardiovascular (CV) risk, in apparent correlation with psoriasis severity. Although less unanimously, evidence of an increased prevalence of CV diseases among psoriasis patients has been reported, including ischemic heart disease, cerebrovascular, peripheral vascular and heart structural disorders. In particular, various studies showed a correlation between psoriasis and major CV events (i.e., myocardial infarction, stroke), while others investigated subclinical changes of blood vessels, such as intima-media thickness increase, arterial stiffness and coronary artery calcification. A series of different mechanisms, like traditional CV risk or iatrogenic risk factors, inflammation, hemostasis dysregulation, hyperhomocysteinemia, and shared genetic susceptibility, are thought to underlie this epidemiological association. Among these elements, inflammation and its related cytokine milieu, including Th1-mediated response and Th17/Treg imbalance, C reactive protein and the newly implicated osteopontin are considered to play a primary role, even if yet to be fully understood.

Infliximab is an anti-tumor necrosis factor-alpha monoclonal antibody that is highly effective for the treatment of psoriatic disease. During maintenance treatment, some patients may experience a disease relapse, and, in such circumstances, dose intensification is frequently used to regain efficacy. We report our cumulative experience on the use of infliximab re-induction in patients whose psoriasis relapsed during long-term maintenance treatment with infliximab. From September 2005 to January 2009, 22 patients required re-induction because of a relapse of their psoriasis. Re-induction was effective in restoring response in most patients and was well tolerated in all cases, without occurrence of serious or unexpected adverse events.

Cod liver oil is a well-known "nutraceutical", which contains a wide range of substances, including triacylglycerols (TAGs), mono- and di-acylglycerols, free fatty acids, vitamins and n-3 polyunsaturated fatty acids. Topically applied, cod liver oil contributes to faster wound healing and improvement in skin quality. We recently reported a case of allergic contact dermatitis to cod liver oil contained in a topical ointment, in whom the patch test reaction with the ointment containing cod liver oil at a concentration of 40% was stronger than the reaction induced by a pure cod liver oil at the same concentration. We hypothesized that the different reactivity could be explained by differences in composition of the two products. In order to verify this hypothesis, we assessed the composition of those products using a matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The results obtained showed that the spectra of the ointment and of the cod liver oil samples were very similar, even if a major number of peaks were observable in the higher mass range of the spectra relevant to the analysis of the ointment sample, that have been assigned to higher molecular weight TAGs. Our results suggest that the different reactivity to the two products could be due to differences in the amount of contained TAGs. TAGs may favor the penetration of the allergen(s) or may be the direct culprit substances, taking into account that TAGs have been reported to have sensitizing properties.

A new class of drugs, produced with the hybridoma technique, has been introduced and employed to treat many immunological diseases. This class consists of recombinant monoclonal antibodies, which can be chimeric, humanized or human. Predictably, there has been a rise in adverse hypersensitivity reactions to these therapeutic agents, whose pathogenic mechanisms are not yet well understood. Specific IgE has been demonstrated in a very few cases, and only in some of these recombinant antibodies. Skin tests are not done as a clinical routine screening. In the present article the mechanisms underlying hypersensitivity reactions to these drugs are analyzed, also in the light of the personal experience and that reported in the literature, with the aim of identifying potential risk factors and means of prevention of these reactions. For some drugs, infusion reactions may be prevented thanks to the the use of premedication. Moreover, symptoms of acute hypersensitivity during infusion can be successfully managed in the majority of cases by slowing the speed of administration. All these findings seem to confirm that the pathogenesis is not related to a true immediate (IgE-mediated) hypersensitivity in most cases. When the substitution of the drug that has triggered a hypersensitivity reaction is required, this is only possible if such an alternative drug exists (i.e., replacement of a chimeric antibody with a humanized or human antibody sharing the same target). As an alternative, desensitization protocols have been employed to induce a state of temporary tolerance to the drug in some cases, yielding successful results for infliximab and trastuzumab.

The management of chronic hand eczema is usually difficult. The aim of this open-label study is to assess the effectiveness and ‘steroid-sparing’ activity of a barrier cream containing polyvinylpyrrolidone in patients with chronic hand eczema. Rescue treatment with topical corticosteroids (TCs) was permitted in the event of eczema worsening, whereas preventive measures were maintained unchanged with respect to those adopted by patients in the past. Among the 207 participants, the main diagnosis was irritant contact dermatitis, followed by allergic contact dermatitis and atopic dermatitis. Nearly half of the patients (49%) applied the barrier cream once or twice a day, while the remaining patients used it three or more times per day. Regardless of rescue therapy with TCs, regular use of the barrier cream caused a progressive significant improvement of eczema severity, as indicated by dermatologists' and patients' assessments. A significant reduction in the amount of the TC applied in the last 3 months and in the number of TC treatment days during the previous 4 weeks was found at the end of 12-week treatment with the barrier cream as compared with baseline. The product was also well-tolerated and accepted by the majority of patients. The results of this study suggest that a barrier cream containing polyvinylpyrrolidone can represent a useful tool in the management of chronic hand eczema and may show steroid-sparing effects.

Signs supporting antiinflammatory effects of H1-antihistamines were first reported long ago, but their clinical relevance remains controversial, especially with respect to their ability to inhibit the release of histamine and other preformed mediators. Experimental studies have documented that H1-antihistamines may affect several inflammatory events, including chemotaxis and the survival of eosinophils, the expression of adhesion molecules, and the release of chemokines and cytokines from different sources, thus highlighting the potential for a modulation of chronic inflammation and immune responses. Interestingly, a specific inhibitory effect on Th2-type cytokine secretion has been demonstrated for some new generation antihistamines. The mechanisms responsible for the antiinflammatory activity of H1-antihistamines are still unclear, but are presumed to be both receptor-dependent and receptor-independent. Recent findings have indicated the ability of these drugs to down-regulate intracellular signaling pathways, i.e., NF-kappaB. In this article, the current knowledge and novel findings about the antiinflammatory action and mechanisms of H1-antihistamines are briefly reviewed and critically analyzed, from the standpoint of possible clinical implications with special reference to skin disorders.

Anti-tumor necrosis factor (TNF) biologic drugs are among the most important advances recently introduced in the treatment of psoriasis. These drugs have modified the traditional view of psoriasis pathogenesis and have changed the approach to the disease and its management. Etanercept and infliximab are the only TNF inhibitors currently approved for plaque psoriasis. Adalimumab is in Phase III trials for this indication. All these drugs are approved for the treatment of psoriatic arthritis. Other TNF-targeting agents are under investigation for psoriasis and other diseases. This article briefly reviews the current knowledge of TNF blockers in psoriasis, with emphasis on pharmacologic profile, mechanism of action, immunogenicity, efficacy, safety, novel aspects related to clinical use (dose, regimens and long-term management) and European and US prescribing guidelines.