Differential diagnosis of contact dermatitis: A practical-approach review by the EADV Task Force on contact dermatitis.

The diagnosis of eczema ('dermatitis') is mostly clinical and depends on the clinical history and exploratory objective findings (primary lesions, patterns). Contact dermatitis remains as an important condition in the group of eczematous disorders, with important socioeconomic and occupational relevance. Although irritant and allergic contact dermatitis have a different pathogenesis, both are characterized by a rather typical morphology, are triggered by external factors and tend to occur primarily in the area of contact with the exogenous agent. In addition, allergic and irritant dermatitis may also co-exist. The importance of diagnosing contact dermatitis, especially when allergic in nature, is both due to the possibility of avoiding the trigger, and due to its role in aggravating other skin conditions. Nevertheless, the heterogeneity of clinical presentations in daily practice may pose an important challenge for the suspicion and correct diagnosis of contact dermatitis. Furthermore, other conditions, with different pathogenesis and treatment, may clinically simulate contact dermatitis. The Task Force aims to conduct a review of the unifying clinical features of contact dermatitis and characterize its main clinical phenotypes, and its simulators, in order to contribute to an early suspicion or recognition of contact dermatitis and enable a correct differential diagnosis.

A Familial Novel Putative-Pathogenic Mutation Identified in Plaque-Psoriasis by a Multigene Panel Analysis.

Psoriasis is a chronic multifactorial skin disorder with an immune basis. It is characterized by patches of skin that are usually red, flaky and crusty, and that often release silvery scales. The patches appear predominantly on the elbows, knees, scalp and lower back, although they may also appear on other body areas and severity may be variable. The majority of patients (about 90%) present small patches known as "plaque psoriasis". The roles of environmental triggers such as stress, mechanical trauma and streptococcal infections are well described in psoriasis onset, but much effort is still needed to unravel the genetic component. The principal aim of this study was to use a next-generation sequencing technologies-based approach together with a 96 customized multigene panel in the attempt to determine if there are germline alterations that can explain the onset of the disease, and thus to find associations between genotypes and phenotypes. To this aim, we analyzed a family in which the mother showed mild psoriasis, and her 31-year-old daughter had suffered from psoriasis for several years, whereas an unaffected sister served as a negative control. We found variants already associated directly to psoriasis in the TRAF3IP2 gene, and interestingly we found a missense variant in the NAT9 gene. The use of multigene panels in such a complex pathology such as psoriasis can be of great help in identifying new susceptibility genes, and in being able to make early diagnoses especially in families with affected subjects.

European Surveillance System on Contact Allergies (ESSCA): Characteristics of patients patch tested and diagnosed with irritant contact dermatitis.

BACKGROUND: Irritant contact dermatitis (ICD) is caused by the acute locally toxic effect of a strong irritant, or the cumulative exposure to various weaker physical and/or chemical irritants. OBJECTIVES: To describe the characteristics of patients with ICD in the population patch tested in the European Surveillance System on Contact Allergies (ESSCA; www.essca-dc.org) database. METHODS: Data collected by the ESSCA in consecutively patch-tested patients from January 2009 to December 2018 were analyzed. RESULTS: Of the 68 072 patients, 8702 were diagnosed with ICD (without concomitant allergic contact dermatitis [ACD]). Hand and face were the most reported anatomical sites, and 45.7% of the ICD was occupational ICD (OICD). The highest proportions of OICD were found in metal turners, bakers, pastry cooks, and confectionery makers. Among patients diagnosed with ICD, 45% were found sensitized with no relevance for the current disease. CONCLUSIONS: The hands were mainly involved in OICD also in the subgroup of patients with contact dermatitis, in whom relevant contact sensitization had been ruled out, emphasizing the need for limiting irritant exposures. However, in difficult-to-treat contact dermatitis, unrecognized contact allergy, or unrecognized clinical relevance of identified allergies owing to incomplete or wrong product ingredient information must always be considered.

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.

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.

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.

Anterior cervical hypertrichosis: a case report and review of the literature.

Anterior cervical hypertrichosis (ACH), or "hairy throat," is a rare form of localized hypertrichosis that refers to the presence of a tuft of terminal hair on the anterior neck. Only 40 cases of ACH have been reported in the literature. Although it is usually an isolated finding, it may be associated with systemic disorders such as neurologic abnormalities (peripheral neuropathy, developmental delay, mental retardation), ophthalmologic disorders (optic atrophy, chorioretinal changes), hallux valgus, and dorsal hypertrichosis. Thus it is strongly advised to take a thorough family history and to perform clinical examinations and investigations (neurologic and ophthalmologic examination, electromyography, X-ray of the feet) in all patients with ACH to exclude possible associated abnormalities. We report the case of a 7-year-old Italian girl who presented with this condition as an isolated finding.

Lack of evidence of viral reactivation in HBsAg-negative HBcAb-positive and HCV patients undergoing immunosuppressive therapy for psoriasis.

BACKGROUND: HBV and HCV reactivation have been widely reported in patients undergoing immunosuppressive therapy (IT); however, few data are available on the risk of reactivation in patients with psoriasis receiving IT. The aim of our study was to assess the prevalence of HBV and HCV infection in patients with psoriasis and to evaluate the effects of IT during the course of the infection. METHODS: The study included psoriatic patients who attended an Italian tertiary referral hospital from 2009 to 2012. A total of 224 patients were enrolled. We evaluated: HBV and HCV markers, type of IT and the occurrence of viral reactivation. The observational period ranged from the beginning of IT to the last visit, with a mean follow-up period of 54 months. RESULTS: Two hundred and twenty patients (135 males and 89 females; mean age 59 years; range 18-86 years) with psoriasis, with or without psoriatic arthritis, receiving conventional IT and/or biological drugs were tested for markers of infection. We identified 23/224 patients (10.2%) with isolated positivity for HBcAb positivity, 36/224 (16%) with positivity for HBsAb/HBcAb, and 15/224 (6.6%) with positivity for HCV-Ab. No patient was HBsAg positive, none of them underwent pre-emptive therapy with lamivudine or other antiviral drugs and no one showed episodes of viral reactivation. CONCLUSIONS: The prevalence of HBsAg in patients with psoriasis is lower than that observed in the general population. The prevalence of isolated positivity for HBcAb and of combined positivity for HBcAb and HBsAb is 10.2% and 16%, respectively. The prevalence of HCV infection (HCV-RNA+) is 4%. In patients with psoriasis and HCV-Ab or HBcAb positivity, the IT seems to be safe, regardless of the type of drugs.

Tacrolimus does not alter the production of several cytokines and antimicrobial peptide in Malassezia furfur-infected-keratinocytes.

Topical immunosuppressant therapy is widely used in the treatment of inflammatory skin diseases, such as atopic dermatitis and psoriasis. Besides its beneficial therapeutic effects, application of topical anti-inflammatory drugs may render the epidermis more vulnerable to invading pathogens by suppressing innate immune responses in keratinocytes (KCs). Cytokines, chemokines and antimicrobial peptides (AMPs) produced by epithelial cells enable them to participate in innate and acquired immune responses. The aim of the present work was to study the influence of tacrolimus (FK506) on KCs infected with Malassezia furfur (M. furfur), evaluating the expression of pro-inflammatory cytokines IL-1α and IL-6, chemokine IL-8, anti-inflammatory cytokines transforming growth factor beta1 (TGF-ß1) and IL-10 and AMP ß-defensin-2. Human KCs were obtained from surgical specimens of normal adult skin. The expression of mRNAs in KCs: FK506-treated, FK506-treated and M. furfur-infected as well as only M. furfur-infected was quantified by real-time quantitative polymerase chain reaction. Next, the production of the AMP ß-defensin-2 and of the above-mentioned pro-inflammatory and anti-inflammatory cytokines was evaluated using enzyme-linked immunosorbent assay. In this study, FK506 did not alter cytokine and AMP production by KCs; this led us to hypothesise that it may not enhance the risk of mycotic skin infections.

Enhanced antioxidant effect of trans-resveratrol: potential of binary systems with polyethylene glycol and cyclodextrin.

Trans-resveratrol, a polyphenol extracted from Vitis vinifera, has different beneficial effects following its administration on the skin. Here the potential use of binary systems to enhance in vitro and in vivo activity of trans-resveratrol was investigated. Thus the aqueous solubility of trans-resveratrol was investigated in the presence of growing concentrations of polyethylene glycol (PEG) or ß-cyclodextrin (ßCD) as solubilizing excipients. Then, the solid dispersion of trans-resveratrol with PEG or inclusion complexes trans-resveratrol/ßCD were prepared and characterised by different methods. Cytotoxicity and inhibition of reactive oxygen species (ROS) following H2O2 challenge in the presence of trans-resveratrol, alone or associated to the excipients, was evaluated on human keratinocyte HaCaT cell line. Both the trans-resveratrol-containing binary systems induced significant reduction of H2O2-induced ROS production, especially in the case of ßCD that was selected for the following phase of the study. Thus, the effect of a cream containing trans-resveratrol, alone or associated to ßCD, on different skin parameters such as corneometry, colorimetry and elastometry, was evaluated on human volunteers. All patients showed a visible improvement of clinical conditions with a remarkable decrease of aging signs, but this effect was higher of the hemi face treated with the ßCD-containing formulation versus formulation containing trans-resveratrol alone.

The balance between pro- and anti-inflammatory cytokines is crucial in human allergic contact dermatitis pathogenesis: the role of IL-1 family members.

The interleukin (IL)-1 family includes 11 members that are important in inflammatory processes. It includes various agonists and two antagonists, IL-1Ra and IL-36Ra. Our aim was to investigate whether the IL-1 family is involved in allergic contact dermatitis (ACD). The expression of IL-1 family members was evaluated by PCR and immunohistochemistry in the positive patch test reaction site (involved skin) and in the uninvolved skin of ACD patients. We also examined these cytokines in an ex vivo model of ACD. The antagonistic activity of IL-36Ra was evaluated by injecting recombinant IL-36Ra in uninvolved skin biopsies of ACD patients. IL-1Ra and IL-36Ra expression was quantified in mononuclear cells of nickel-sensitized patients challenged in vitro with nickel. IL-33 involvement in ACD was investigated by intra-dermal injection of anti-IL-33 in the uninvolved skin of patients ex vivo. Results showed that IL-1ß, IL-1Ra, IL-36α, IL-36ß, IL-36γ and IL-33 expression, but not IL-36Ra expression, was enhanced in ACD-involved skin. Immunohistochemical analysis and ex vivo skin cultures confirmed these results. Injection of anti-IL-33 in ACD-uninvolved skin inhibited IL-8 expression, whereas IL-36Ra inhibited IL-36α, IL-36ß, IL-36γ and IL-8 expression. Nickel induced IL-1Ra expression in lymphocytes of nickel-sensitized patients. Hence, various IL-1 agonists and antagonists may be involved in ACD pathogenesis.

Periungual and subungual pyogenic granuloma following anti-TNF-α therapy: is it the first case?

Tumor necrosis factor-alpha (TNF-α) antagonists have advanced treatment of psoriasis and other chronic inflammatory diseases but are not free of adverse effects. Pyogenic granuloma is yet described in literature as a dermatological side effect of multiple drugs such as retinoids, antiretroviral, and antineoplastic drugs but, to the best of our knowledge, it has never been reported among the adverse skin reactions following anti-TNF-α therapy. We report on a 20-year-old Caucasian man with psoriatic arthritis who developed multiple eruptive periungual and subungual pyogenic granulomas following treatment with TNF-α antagonist etanercept.

IL-33 is secreted by psoriatic keratinocytes and induces pro-inflammatory cytokines via keratinocyte and mast cell activation.

IL-33 is a novel pro-inflammatory cytokine and ligand for the orphan receptor ST2. Although originally defined as an inducer of Th2-mediated responses, IL-33 was recently found to be involved in arthritis, a Th1/Th17-mediated disease. Here, we assessed the ability of IL-33 to promote inflammation via mast cells (MCs) and keratinocytes (KCs) activation in psoriasis. IL-33 resulted elevated in the skin but not in the serum of psoriasis patients. IL-33 was secreted by psoriasis KCs and HaCaT cells after TNF-α stimulation. In HMC-1, TNF-α, but not IL-17, could induce a robust increase in IL-33 expression. In HaCaT cells, TNF-α was able to induce IL-6, MCP-1 and VEGF, and the addition of IL-33 reinforced these increases. TNF-α + IL-33 combination showed similar results in primary KCs and ex vivo skin organ culture. In conclusion, our study suggests that IL-33 may be involved in psoriasis biology via MCs and KCs.

Psoriatic disease and tuberculosis nowadays.

Psoriasis is a chronic, relapsing and remitting inflammatory skin and joint disease that has a prevalence of 2-3% in the world's population, whereas of 1-2% in Europe. The traditional concept of psoriasis as the "healthy people's" disease has been recently revised because of ever-increasing reports of associations with various pathological conditions (hypertension, Crohn's disease, type II diabetes mellitus, obesity, dyslipidemia, metabolic syndrome, infectious conditions). Particularly, advances in psoriasis therapies have introduced biologic agents. All the tumor necrosis factor-alpha inhibitors are associated with an increased risk of developing active disease in patients with latent tuberculosis infection, because of TNF-α key role against Mycobacterium tuberculosis. For this reason, exclusion of active tuberculosis and treatment of latent tuberculosis infection are clinical imperatives prior to starting this therapy. Moreover active surveillance for a history of untreated or partially treated tuberculosis or latent form has already been shown to be effective in reducing the number of incident tuberculosis cases.

Current patch test results with the European baseline series and extensions to it from the 'European Surveillance System on Contact Allergy' network, 2007-2008.

BACKGROUND: The pattern of contact sensitization to the supposedly most important allergens assembled in the baseline series differs between countries, presumably at least partly because of exposure differences. Objectives. To describe the prevalence of contact sensitization to allergens tested in consecutive patients in the years 2007 and 2008, and to discuss possible differences. METHODS: Data from the 39 departments in 11 European countries comprising the European Surveillance System on Contact Allergy network (www.essca-dc.org) in this period have been pooled and analysed according to common standards. RESULTS: Patch test results with the European baseline series, and country-specific or department-specific additions to it, obtained in 25 181 patients, showed marked international variation. Metals and fragrances are still the most frequent allergens across Europe. Some allergens tested nationally may be useful future additions to the European baseline series, for example methylisothiazolinone, whereas a few long-term components of the European baseline series, namely primin and clioquinol, no longer warrant routine testing. CONCLUSIONS: The present analysis points to 'excess' prevalences of specific contact sensitization in some countries, although interpretation must be cautious if only few, and possibly specialized, centres are representing one country. A comparison as presented may help to target in-depth research into possible causes of 'excess' exposure, and/or consideration of methodological issues, including modifications to the baseline series.

Safety of anti-TNFα agents in the treatment of psoriasis and psoriatic arthritis.

CONTEXT: The efficacy and favorable safety profile of anti-tumor necrosis factor (TNF) agents in the treatment of psoriasis and psoriatic arthritis (PsA) are supported by several randomized controlled studies and meta-analyses. However, some concerns on the long-term safety of these drugs still exist, as these studies generally included small patient numbers and were performed in selected patient populations. OBJECTIVE: This review presents and discusses current evidence on the safety of anti-TNFα agents in patients with psoriasis and PsA, with a focus on European registry studies and case reports of particular importance. METHODS: Key studies on the safety of anti-TNFα agents in the treatment of adult patients with psoriasis or PsA were identified by a MEDLINE search (last updated 10 November 2011) based on several interrelated queries, with a focus on European registries. Other studies and case reports were included if deemed relevant. Studies concerning other conditions, such as rheumatoid arthritis (RA), were included as appropriate when data in psoriatic disease were unavailable or insufficient. RESULTS: Available data on the safety of anti-TNFα agents such as etanercept in psoriasis and PsA appear reassuring, even if some concerns still exist. Most notably, data suggest a higher incidence of infection and lymphoma amongst patients treated with the anti-TNFα monoclonal antibodies infliximab and adalimumab compared with etanercept. CONCLUSION: The overall safety profile of monoclonal antibodies in patients with psoriasis, PsA and RA seems less favorable than that of etanercept, particularly in terms of risk of infection and hepatotoxicity.

Increased cysteinyldopa plasma levels hint to melanocyte as stress sensor in psoriasis.

The possible role of melanocyte as a modulator of the inflammation and keratinocyte hyperproliferation in psoriasis has been hypothesised but never demonstrated on experimental basis. Aim of the present study was to assess whether plasma levels of 5-S-cysteinyldopa (CD), a metabolite reflecting melanocyte activity, undergo changes in association with psoriasis together with those of typical lipid peroxidation markers thiobarbituric acid reactive substances (TBARS). A group of 16 patients with psoriasis at different stage as indicated by the psoriasis area and severity index (PASI) were enrolled against an age and sex matched control group. Both TBARS (P<0.05) and CD (P<0.005) levels were higher than controls with statistical significance. After 1 month therapy the levels of either biomarkers decreased with respect to the starting values although with marked individual differences. CD may represent a novel and sensitive biomarker for the follow up of psoriasis and evaluation of the efficacy of therapeutic regimens beyond PASI determination.

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.

Quantitative determination of haptoglobin glycoform variants in psoriasis.

Haptoglobin is an acute phase glycoprotein, secreted by hepatocytes and other types of cells including keratinocytes. Haptoglobin has been suggested to impair the immune response, inhibit gelatinases in the extracellular matrix and promote angiogenesis, but its role in psoriasis is obscure to date. Changes in haptoglobin glycan structure were observed in several diseases. The aim of this study was to investigate whether haptoglobin displays glycan variations in psoriasis. We found that the pattern of plasma haptoglobin glycoforms, following two-dimensional electrophoresis, exhibited significant quantitative differences in spot intensities between patients and controls. Quantitative and qualitative differences in glycan mass, between patients and controls, were found by mass spectrometry of glycopeptides from tryptic digests of protein isolated from both patients and controls. The number of distinct fucosylated glycoforms of peptides NLFLNHSENATAK and MVSHHNLTTGATLINEQWLLTTAK was higher in patients than in controls, but no fucosylated glycan was detected on peptide VVLHPNYSQ-VDIGLIK in either case. The number of peptides with distinct triantennary and tetraantennary glycans was higher in patients than in controls. Abundance or structure of specific glycans, which are present in haptoglobin from patients and are different or missing in normal haptoglobin, might be associated with disease activity.