Diagnosis and treatment of classic and iatrogenic Kaposi's sarcoma: Italian recommendations.

Kaposi's sarcoma (KS) is a lymphangioproliferative disorder associated with Human herpesvirus 8 (HHV8) infection. Four clinical subtypes are recognized: classic, endemic, epidemic (HIV-related) and iatrogenic. KS diagnosis is based on clinical features, histopathological assessment, and HHV8 serology. Classic KS is usually skin-limited and has a chronic course, while the iatrogenic variant may show mucosal, nodal or visceral involvement. Clinical staging is fundamental to guide the management. Localized disease may be treated with different local therapies, even if there are no randomized trials comparing these different modalities. Aggressive, disseminated KS and cases with visceral involvement usually require systemic chemotherapy, most commonly vinblastine, bleomycin or paclitaxel. Iatrogenic KS needs immunosuppression tapering/withdrawal and, if possible, switch to m-TOR inhibitors in post-transplant KS. The present work by a panel of Italian experts provides guidelines on KS diagnosis and management based on a critical review of the literature and a long and extensive personal experience.

Paraoxonases and psoriasis: negative imbalance of antioxidant endogenous mechanisms.

BACKGROUND: Numerous reports have shown that psoriasis patients are more exposed to lipoprotein peroxidation and to a decrease in the activity of paraoxonase (PON)1, an antioxidant and anti-inflammatory enzyme. Thus, it has been suggested that malfunction of the antioxidant system and an increased production of reactive oxygen species drive immune inflammatory events, that result in progressive skin cell damage in patients with psoriasis. The PON protein family, including PON1, PON2 and PON3, is one of the most important endogenous defense mechanisms against oxidative stress. In the present study, we investigated PON gene expression in psoriasis and in cutaneous oxidative stress. METHODS: The study population included 10 patients affected by moderate-to-severe plaque psoriasis and 15 healthy donors who have undergone to plastic surgery, were used as control. Skin punch biopsies of lesional and non lesional psoriatic skin were performed for analysis of PON2 and PON3 gene expression. In addition, oxidation assays in ex vivo full-thickness healthy skin organ cultures were performed. RESULTS: No significant differences were observed between PON2 and PON3 gene expression in psoriatic lesional and non lesional skin compared with healthy controls. H2O2 treatment induced a significant decrease of PON2 and PON3 expression in ex vivo full-thickness healthy skin organ cultures; conversely the pretreatment of samples with the antioxidant reagent N-acetyl-L-cysteine (NAC) induced a significant increase. Interestingly, no significant alterations were reported for PON2 and PON3 expression in ex vivo full-thickness healthy skin organ cultures stimulated with IL-17. CONCLUSIONS: Taken together our findings have revealed that a strong pro-oxidative activity is not effectively countered by antioxidant endogenous mechanisms both in psoriatic skin and in ex vivo experimental model.

Multidisciplinary Management of Spondyloarthritis-Related Immune-Mediated Inflammatory Disease.

INTRODUCTION: Immune-mediated inflammatory diseases (IMIDs) are chronic autoimmune conditions that share common pathophysiologic mechanisms. The optimal management of patients with IMIDs remains challenging because the coexistence of different conditions requires the intervention of several specialists. The aim of this study was to develop a series of statements defining overarching principles that guide the implementation of a multidisciplinary approach for the management of spondyloarthritis (SpA)-related IMIDs including SpA, psoriasis, psoriatic arthritis, Crohn's disease, ulcerative colitis and uveitis. METHODS: A Delphi consensus-based approach was used to identify a core set of statements. The process included development of initial questions by a steering committee, an exhaustive search of the literature using complementary approaches to identify potential statements and two Delphi voting rounds for finalization of the statements. RESULTS: Consensus was achieved on the related nature of IMIDs, the existence of a high prevalence of multiple IMIDs in a single patient and the fact that a multidisciplinary approach can result in a more extensive evaluation and comprehensive approach to treatment. The goals of a multidisciplinary team should be to increase diagnosis of concomitant IMIDs, improve the decision-making process, and increase patient satisfaction and adherence. Early referral and diagnosis, early recognition of concomitant IMIDs and optimizing treatment to improve patient quality of life are some of the advantages of using multidisciplinary teams. To be effective, a multidisciplinary team should be equipped with the appropriate tools for diagnosis and follow-up, and at a minimum the multidisciplinary team should include a dermatologist, gastroenterologist and rheumatologist; providing psychologic support via a psychologist and involving an ophthalmologist, general practitioners and nurses in multidisciplinary care is also important. CONCLUSION: The present Delphi consensus identified a set of overarching principles that may be useful for implementation of a multidisciplinary approach for the management of SpA-related IMIDs. FUNDING: Aristea and Hippocrates.

Topical non-occlusive polymers in hand-foot syndrome.

BACKGROUND: Many cytotoxic and biological drugs are cause of severe dermatological side effects, such as hand-foot syndrome (HFS) and hand-foot skin reaction (HFSR). Oncologic patients with HFS or HFSR presents relevant symptoms that interferes with daily activities and with adherence to anticancer treatment. The HFRS control and treatment are important goals to enhance the quality of life of oncologic patients. The aim of this study was to assess the efficacy and tolerability of a b.i.d. (bis in die) topical administration of an anhydric ointment based on topical non-occlusive polymers (TNOP) in patients with HFS on current anticancer drug regiments. METHODS: A prospective, open, multicenter clinical study was conducted in oncologic patients with HFS attended two hospital-based Italian dermatological unit. A global-non-instrumental evaluation, based on different standardized tools (i.e., Sum Score System Index [SRRC] Score, Dermatology Life Qualiy Index [DLQI] and global efficacy) was conducted using measurements at baseline, at 4 and 8 weeks. Non-parametric test for two correlate samples, was used to assess changes in means of the different scores. The protocol was approved by ethical committee of both dermatology service pariticipating to the study. RESULTS: Twenty-one oncologic patients were enrolled. Thirteen (61.9%) of participants were female. The median age was 63 years (range: 37-73). Seventeen (80.9%) patients presenting a HFS associated to capecitabine, and four patients (19.1%) associated to docetaxel. At the enrollment, 33.3% (7/21) of patients showed at level of the hands a HFS of grade 2 and 9.5% (2/21) of grade 3. At level of the feet, 28.6% (6/21) showed a HFS of grade 2, and 17.4% (4/21) of grade 3. The SRRC scores were significantly decreased after 8 weeks of treatment compared to baseline, for both sites. In particular, SRRC score decreased from 4.38 to 1.67 (Z=-3.60, P=0.00) and from 4.48 to 1.43 (Z=-3.87, P=0.00) for hands and feet, respectively. A consistent significant improvement in the perceived QoL of patients was also observed. From baseline to visit 3, the total mean score of DLQI decreased from 10.62 to 4.57 (Δ=-57%, Z=-4.020, P=0.000). CONCLUSIONS: In a sample of oncologic patients with HFS, the b.i.d. administration of TNOP for eight weeks, induced a progressive and significant decrease of the SRRC Score and a relevant improvement in the perceived quality of life.

Multiple sclerosis following anti-tumor necrosis factor-alpha therapy for psoriasis: first case in Italy?

The use of tumor necrosis factor alpha (TNF-α) antagonists has greatly improved clinical management of psoriasis and other inflammatory diseases, but acute and chronic adverse reactions, including demyelination, are becoming increasingly recognized. We reported a case of multiple sclerosis in a 48-year-old Italian man with plaque psoriasis treated with etanercept. Through a literature review, we found a total of 35 psoriatic patients, including our case, in whom a demyelinating disease developed in course of TNF-α antagonists therapy. Since neurological disorders are rarely associated with the use of anti-TNF-α therapy in psoriatic patients, but have severe side effects, physicians should screen patients before starting therapy, excluding a positive anamnesis for demyelinating disease; if patients receiving anti-TNF-α drugs develop new or unusual neurological symptoms, the anti-TNF-α should be stopped and patients should be properly examined. Furthermore, therapies for demyelinating diseases that could exacerbate psoriasis manifestations should be carefully avoided.

Minimal disease activity in patients with psoriatic arthritis treated with ustekinumab: results from a 24-week real-world study.

Psoriatic arthritis (PsA) is a chronic inflammatory joint disease affecting around 40% of psoriasis patients. Minimal disease activity (MDA) criteria have been proposed to identify a state of low disease activity, one of the principal goals of treatment for psoriatic disease. This study investigated treatment with ustekinumab (UST) in the context of a real-world setting. Thirty-four PsA patients who had failure or inadequate response to conventional synthetic disease-modifying antirheumatic drugs or to anti-tumour necrosis factor alpha were enrolled. Demographic and clinical features, MDA criteria, and the impact of psoriatic skin manifestations on patients' quality of life (QoL) using the dermatology life quality index (DLQI) questionnaire were evaluated at baseline and after 24-week treatment. Adverse events were recorded. At week 24, 70.5% of patients (n = 24) achieved MDA. A sub-analysis of dermatological indices of the MDA criteria showed that the psoriasis area severity index score was significantly improved and body surface area was significantly decreased at 24 weeks compared with that at baseline (both p < 0.001). For the rheumatologic indexes, tender joint count, swollen joint count, and tender entheseal points were all significantly improved at 24 weeks of therapy (all p < 0.01 vs. baseline). Mean DLQI value decreased approximately fourfold, and there were no safety concerns. The achievement of MDA as well as the significant improvement in DLQI and lack of adverse events in the context of a real-life setting shown here confirms the efficacy and safety of UST in PsA.

Psoriatic cutaneous inflammation promotes human monocyte differentiation into active osteoclasts, facilitating bone damage.

Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy that can be associated with focal bone erosions. Psoriasis usually precedes the psoriatic arthritis onset by an average of 10 years, but this relation is not yet fully elucidated. Pro-inflammatory cytokines, such as IL-33, OPN, IL-17, and TNF-α are involved in both psoriasis and PsA pathogenesis as well as in bone homeostasis. In this study, we have demonstrated that IL-33, OPN, IL-17, and TNF-α induced the release of a wide range of pro-osteoclastogenic factors from the skin, such as RANKL, that promote monocyte differentiation in osteoclasts. The addition of osteoprotegerin, a RANKL inhibitor, to monocyte cultures treated with supernatant from stimulated skin did not completely deplete osteoclast formation, suggesting that skin produced several additional pro-osteoclastogenic mediators, which could act in a RANKL-independent manner. Moreover, we have found that RANKL serum levels as well as osteoclast number and activity in psoriatic patients with and without arthritis, was influenced by severity of cutaneous disease. Our data demonstrate that psoriatic cutaneous inflammation contributes to bone damage.

Psoriasis in melanoma patients: a prospective pilot study.

BACKGROUND: Melanoma is an immunogenic tumor and the presence of T-cell infiltrates within melanoma lesions may correlated with longer patient survival. Psoriasis is a chronic immune-mediated inflammatory disease, in which the role of T-cells is well established. The aim of our prospective pilot study was to investigate the relationship between melanoma and psoriasis examining 3 groups of patients: the melanoma-group (MG), the psoriasis-group (PG) and the control-group (CG). METHODS: Every patient underwent detailed anamnestic and clinical examination. Moreover, gene expression of interleukin-6 (IL-6), interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) was analyzed in all groups and in subjects affected by both melanoma and psoriasis (MP). RESULTS: Melanoma patients showed a lower frequency of psoriasis and positive family history (FH) of psoriasis respect to CG. Moreover, psoriatic patients presented fewer MN, and lower frequency of positive FH of melanoma than CG. IL-6 and IFN-γ were significantly increased in PG and reduced in MG. CONCLUSIONS: We propose a provocative hypothesis of a possible protective role of psoriasis for melanoma development.

Chronic hand eczema: is IL-36α helpful in diagnosis and classification?

BACKGROUND: Chronic hand eczema (CHE) is not a homogenous disease, necessitating complex differential diagnostics. Interleukin (IL) -1 family members are significantly up-regulated in ACD and psoriasis patients skin. METHODS: The present study aims to deepen the knowledge about clinical assessment and characterization of patients affected by chronic hand dermatitis (CHD) as well as to investigate the role of possible biomarkers which may help in the diagnostic process. An observational case-control study was performed enrolling 30 CHD patients and 20 healthy controls. Each patient underwent detailed medical history, clinical examination, epicutaneous patch test, and lesional skin biopsies for histological and immunohistochemical analysis. RESULTS: Patient history, clinical examination and patch testing led us to a final CHD characterization in only 8/30 subjects (26.7%). In the remaining subjects, clinical and histological features suggested a diagnosis of psoriasis in 9/22 (30%) and idiopathic chronic hand eczema (CHE) in 13/22 (43.3%). Trying to find a possible marker for the latter dermatosis, we analyzed IL-1 family in all the recruited subjects. IL-1 members were increased in all conditions, but IL-36α was the only analyzed cytokine able to characterize patients who end up with a diagnosis of idiopathic CHE. CONCLUSIONS: In conclusion, we can assess that medical history and patch testing remain essential investigations in CHD patients even if not always sufficient to perform a final diagnosis. Moreover, IL-1 members are probably involved in CHE skin inflammation, with IL-36α being a possible future biomarker which might help in the complex diagnostic process of CHE.

Systemic Treatment of Pediatric Psoriasis: A Review.

Psoriasis is a chronic, immune-mediated, inflammatory skin disease, affecting 1-3% of the white population. Although the existence of two psoriasis incidence peaks has been suggested (one in adolescence before 20 years of age and another in adulthood), its onset may occur at any age, including childhood and adolescence, in which the incidence is now estimated at 40.8 per 100,000. As for adult psoriasis, pediatric psoriasis has recently been associated with obesity, metabolic syndrome, increased waist circumference percentiles and metabolic laboratory abnormalities, warranting early monitoring and lifestyle modifications. In addition, due to psoriasis' chronic nature and frequently occurring relapses, psoriatic patients tend to have an impaired quality of life, often requiring long-term treatment. Therefore, education of both pediatric patients and their parents is essential to successful and safe disease management. Given the lack of officially approved therapies, the very limited evidence-based data from randomized controlled trials, and the absence of standardized guidelines, to date, pediatric psoriasis treatment is primarily based on published case reports, case series, guidelines for adult psoriasis, expert opinions and experience with these drugs in other pediatric disorders coming from the disciplines of rheumatology, gastroenterology and oncology. This review focuses on the use of systemic treatments in pediatric psoriasis and their specific features, analyzing the few literature evidences available, expanding the treatment repertoire and guiding dermatologists in better managing of recalcitrant pediatric psoriasis.

Prevalence of acute and chronic viral seropositivity and characteristics of disease in patients with psoriatic arthritis treated with cyclosporine: a post hoc analysis from a sex point of view on the observational study of infectious events in psoriasis complicated by active psoriatic arthritis.

BACKGROUND: Sex medicine studies have shown that there are sex differences with regard to disease characteristics in immune-mediated inflammatory diseases, including psoriasis, in immune response and susceptibility to viral infections. We performed a post hoc analysis of the Observational Study of infectious events in psoriasis complicated by active psoriatic arthritis (SYNERGY) study in patients with psoriatic arthritis (PsA) treated with immunosuppressive regimens including cyclosporine, in order to evaluate potential between-sex differences in severity of disease and prevalence of viral infections. METHODS: SYNERGY was an observational study conducted in 24 Italian dermatology clinics, which included 238 consecutively enrolled patients with PsA, under treatment with immunosuppressant regimens including cyclosporin A. In this post hoc analysis, patients' demographical data and clinical characteristics of psoriasis, severity and activity of PsA, prevalence of seropositivity for at least one viral infection, and treatments administered for PsA and infections were compared between sexes. RESULTS: A total of 225 patients were evaluated in this post hoc analysis, and 121 (54%) were males. Demographic characteristics and concomitant diseases were comparable between sexes. Statistically significant sex differences were observed at baseline in Psoriasis Area and Severity Index score (higher in males), mean number of painful joints, Bath Ankylosing Spondylitis Disease Activity Index, and the global activity of disease assessed by patients (all higher in females). The percentage of patients with at least one seropositivity detected at baseline, indicative of concomitant or former viral infection, was significantly higher among women than among men. No between-sex differences were detected in other measures, at other time points, and in treatments. Patients developed no hepatitis B virus or hepatitis C virus reactivation during cyclosporine treatment. CONCLUSION: Our post hoc sex analysis suggests that women with PsA have a greater articular involvement and a higher activity of disease compared to males. Immunosuppressive treatment with cyclosporine seems not to increase susceptibility to new infections or infectious reactivations, with no sex differences.

Aquagenic wrinkling of the palms: a case report and literature review.

Aquagenic wrinkling of the palms (AWP) is an unusual and rare dermatological condition characterized by excessive palmar wrinkling, occurring within a few minutes of water exposure. Cystic fibrosis (CF) or CF carrier state associated forms, drug induced cases, and idiopathic forms have been described. We report the case of a 27-year-old woman with a 7-year history of transient excessive wrinkling of her palms after brief exposure to water. We present also a comprehensive review of the literature. We believe that AWP has been underdiagnosed thus far and we would like to encourage investigations such as sweat chloride test or genetic studies in these patients because of the association with CF or CF carrier state, particularly when AWP appears in younger ages.

How to treat actinic keratosis? An update.

Actinic keratosis (AKs) is one of the most common skin lesions leading to an increased risk of developing squamous cell carcinoma and other skin malignancies. The lesions principally arise as a result of excessive ultraviolet (UV) exposure. AKs may regress spontaneously, remain stable or evolve to invasive squamous cell carcinoma. The risk of squamous cell carcinoma is significantly increased patients with more than 5 AKs. The main mechanisms involved in the formation of AK are inflammation, mutagenesis, oxidative stress, impaired apoptosis, immunosuppression, disregulation of cell growth and proliferation, and tissue remodeling. Human papilloma virus has also been correlated with the formation of some AKs. As an individual ages, his skin is exposed to increasing cumulative amounts of UV light and other environmental insults. This is especially true for the head, neck and forearms. These insults do not target only the skin where individual lesions develop, but also the surrounding area. In this area undetectable preclinical AK lesions or dysplastic cells may be present. The whole affected area is known as the 'field'. Therefore, management is divided into lesion-directed and field-directed therapies. Currently, the therapies in use are lesion-directed cryotherapy and/or excision, and field-directed topical agents: 5-fluorouracil, diclofenac, photodynamic therapy, imiquimod, and ingenol mebutate. Combining lesion- and field-directed therapies showed good results and several novel therapies are under investigation. Treatment is variable and personalized, what makes a gold standard management algorithm difficult to design. This review aims to describe the rationale behind the available treatment options for AKs based on current understanding of pathophysiology and epidemiology.

New strategies to address the pharmacodynamics and pharmacokinetics of tumor necrosis factor (TNF) inhibitors: A systematic analysis.

AIM: To assess the putative link between antibody formation to adalimumab, infliximab and etanercept, circulating drug levels and clinical outcomes. METHODS: A literature search was conducted using Pubmed from inception to 5th March 2013 of original research articles relating to adalimumab, etanercept and infliximab that investigated the immunogenicity of each drug. Data were extracted to document the disease, anti-TNF-α agent, regimen, study design, use of concomitant immunosuppressive therapy, the relationship between drug administration and antibody assessment, the type of immunoassay and cut-off, plasma drug concentration, frequency of antibody and clinical assessments, antibody positivity rate and relationship between antibody positivity and clinical outcome. Studies were stratified by drug, disease area and whether or not concomitant immunosuppressive therapy had been given. All data were tabulated by publication and analyzed descriptively. RESULTS: A total of 57 original research articles were included in the analysis (infliximab n=34; adalimumab n=18; etanercept n=5). There was considerable heterogeneity in study design, methodology for anti-drug antibody detection and drug bioavailability evaluation. Consequently, it was difficult to compare the immunogenic potential of infliximab, adalimumab and etanercept, particularly because different assays with variable sensitivity and specificity were used. The timing of occurrence and the persistence of anti-drug antibodies appeared to be influenced by administration schedules and concomitant immunosuppressive therapy. Monitoring of circulating drug levels and anti-drug antibodies appears to be an emerging and cost-effective strategy for the management of the individual patient. CONCLUSIONS: Monitoring drug and anti-drug antibody levels appears to be a putative strategy for optimal and cost-effective intervention. However studies of consistent and homogeneous design, methodology and duration are warranted to assess the true incidence and consequences of immunogenicity.

High-resolution color-Doppler ultrasound for the study of skin growths.

UNLABELLED: High-resolution (17 MHz) color-Doppler ultrasound (US) is used in the evaluation of normal and pathological skin. To analyze retrospectively the sonographic pattern of healthy skin and of some skin lesions using Doppler US and to compare the results with dermoscopy examination and histology to identify specific patterns of ultrasound for differentiating benign from malignant lesions. To select among them the Melanomas to describe their US pattern, the presence and morphology of vascular signal and to compare their thickness at US with the Breslow index. After signing informed consent in accordance with the ethical standards laid down in the Declaration of Helsinki in 1964 and its subsequent amendments, 104 patients with skin lesions were retrospectively studied. Patients were evaluated with clinical dermatological examination and Doppler US, and underwent surgical excision with subsequent histological analysis. STATISTICAL ANALYSIS: the difference between variables was analyzed with statistical Chi square test or Fisher's when appropriate. The strength of the relationship between variables was analyzed with Pearson's r coefficient. The sensitivity and specificity of US tests were also calculated. Sixty-five malignant lesions and 39 benign lesions were identified at Doppler US. In the 34 melanomas, typical US and vascular patterns were identified depending on the thickness of the lesion and a strong correlation between the latter and Breslow index was confirmed. Doppler US is a valuable diagnostic tool for the study of skin and for pre-excision characterization of skin lesions.

Psoriasis and skin pain: instrumental and biological evaluations.

The prevalence of skin pain and the molecular mechanisms responsible for pain in psoriasis remain unclear. This study assessed skin pain in 163 patients (98 males, 65 females, range 18-81 years) with plaque psoriasis, evaluating: the subjective/objective features of this symptom compared with clinical severity of the disease; and the role of interleukin (IL)-33, (involved in both psoriasis and pain pathogenesis), in psoriasis-related pain. Clinical measures used were a questionnaire, plaque Physician Global Assessment (PGA) index, pressure algometry to measure pain threshold and tactile/thermal sensitivity test. IL-33 gene expression was examined in vivo (n = 12) in patients skin and through an ex vivo model of nociception using sodium dodecyl sulphate. Of the psoriatic patients 43.6% reported skin pain during the previous week; itchy, unpleasant, aching, sensitive, hot/burning, tender and cramping were the most reported qualities. Patients' pain threshold decreased with increasing PGA index and pain intensity. Sensitivity to touch/heat was reduced in lesional skin, compared with unaffected psoriatic skin. IL-33 expression was increased in lesional skin of patients reporting pain and in the ex vivo system. In conclusion, symptoms of skin pain should be taken into account in the management of psoriasis.

Efficacy, tolerability and safety of switching from etanercept to infliximab for the treatment of moderate-to-severe psoriasis: A multicenter, open-label trial (TANGO).

Biologic anti-tumor necrosis factor-α (anti-TNF-α) therapies have revolutionized the management of psoriasis. However, despite similar mechanisms of action, inter-patient variability in the clinical responses to therapy remain unexplained. Possible differences between agents include stability or bioavailability and anti-drug antibody development, and patient factors such as compliance may play a role. As a result, it is not uncommon for physicians to switch a patient from one anti-TNF-α agent to another when initial response is inadequate. This multicenter, single-arm, observational, Phase IV study assessed the efficacy and safety of infliximab therapy in patients with moderate-to-severe psoriasis who had not responded to 24 weeks' etanercept treatment. Drug efficacy was assessed using specific psoriasis indexes; health-related quality of life (HRQoL) was measured using the Dermatology Life Quality Index and the Skindex-29. A total of 48 patients were screened, 38 were treated with infliximab and 31 completed the study. Of these, 71% achieved Psoriasis Area and Severity Index 75 after 10 weeks, and improvement in HRQoL was documented. The results of this study showed that patients with moderate-to-severe psoriasis could be successfully switched from etanercept to infliximab, with improvements in both clinical parameter and HRQoL.

Is cigarette smoking dangerous for chronic hand eczema in housewives?

BACKGROUND: Chronic hand eczema is defined as a persistent (>6 months' duration) noninfectious skin inflammation of the hands. It is twice as common in women as men. Although genetic factors have been considered, greater exposure of women to wet work, such as housework, is assumed to be the most likely explanation. It has been debated whether lifestyle factors may be associated with chronic hand eczema. OBJECTIVE: The objective of this study was to evaluate the influence of cigarette smoking on housewives for the development of chronic hand eczema. METHODS: We analyzed 516 housewives 18 years or older. Two hundred fourteen were affected by chronic hand eczema, and 302 were control subjects. Both patients and control subjects were divided into 2 subgroups, smokers and nonsmokers. An anonymous questionnaire was submitted to each woman. CONCLUSIONS: No significant differences emerged between "smokers" and "nonsmokers" concerning the incidence of chronic hand eczema. In addition, the smokers were mainly affected by a milder ("almost clear") form of the disease. On the other hand, "severe" forms of chronic hand eczema might be more frequent in nonsmokers when compared with smokers. This study suggests that smoking is not associated with onset of chronic hand eczema, but with less severe chronic hand eczema.

IL-33 is regulated by TNF-α in normal and psoriatic skin.

Interleukin-33 (IL-33) is the most recently discovered IL-1 family member. Considered an endogenous "alarmin" released by necrotic cells in response to tissue injury or damage, IL-33 is constitutively expressed in tissues exposed to the environment, where endothelial and epithelial cells constitute its major sources. Several findings reported that pro-inflammatory stimuli, such as IFN-γ and TNF-α, as well as IL-17, can induce IL-33 expression in normal human epidermal keratinocytes. In the present study, we deeply investigated the relation between IL-33 and TNF-α, by employing the whole skin as study model. TNF-α dose- and time-dependently induced IL-33 gene expression in ex vivo healthy skin organ culture. Similarly, TNF-α significantly increased IL-33 mRNA expression in normal human epidermal sheets. Moreover, IL-33 was enhanced in psoriatic skin and anti-TNF-α therapy was able to significantly reduce it. The biology of IL-33 is gaining in complexity, and this molecule is now known to have additional roles beyond its original description. In particular, we can assess that IL-33 is regulated by TNF-α in normal and psoriatic skin.