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.

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.

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.

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.

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.

Contact sensitization of children: a two-decade years history in Naples.

BACKGROUND: Contact sensitization (CS) and allergic contact dermatitis (ACD) were once thought to be rare in children. The aim of our study was to assess CS and ACD in children affected by eczematous conditions referring to our contact and occupational dermatoses service, and to compare the obtained data to the results of a similar study performed in our Department in late Eighties. METHODS: A retrospective analysis of Patch Test data from the Database of Contact Allergy of the Department of Dermatology, University Federico II of Naples, was performed. Moreover results were compared to previous data recorded and analyzed in our center. RESULTS: Of the 416 examined patients, tested during 2005-2010 with the pediatric series, 37.5% developed at least one positive reaction, 15.4% was diagnosed with ACD. The most common allergen was nickel sulphate (16.8%) and the most frequently involved body sites were head and neck (16.3%). Compared to the 1989 study data, our current results highlighted an increase of CS (P<0.001) and ACD diagnosis (P<0.01). CONCLUSIONS: ACD and CS are significantly increased during the last 20 years in our young patients population. The widespread chemical use and premature adult-like attitude may be responsible for earlier and extended exposure to sensitizers.

Psoriasis and high school students: an educational approach.

BACKGROUND: To date, no study evaluating the knowledge of psoriasis among high school students has been conducted. Thus, we aimed to examine the awareness of such disease among teenagers as well as the possible changes in both the perception of psoriasis and comprehension level after an interactive lesson. METHODS: A school-based survey was conducted in March 2016 on 300 high school students aged 14-18 years. The survey followed a three-step process. Initially, the questionnaire was administered to students in a 30 minutes period. Subsequently, a dermatologist held a lesson of 120 minutes on various features of psoriasis. Few hours after the presentation, the same questionnaire was re-administered to the same students in order to assess the degree of learning. RESULTS: Two-hundred and fifty students completed the survey. In the prelesson evaluation, the mean score was 5.9±4.5 (range 0-14). Students improved their baseline scores by an average of 6.3 points in the absolute score in the postlessons questionnaire results (mean value =12.2±1.9). Scores gained in postlesson test were statistically significant improved compared to prelesson examination (P<0.001). CONCLUSIONS: Our study demonstrated that psoriasis awareness among young subjects is very low and needs to be increased, through specific educational programs.

Acute Localized Exanthematous Pustulosis (ALEP): Review of Literature with Report of Case Caused by Amoxicillin-Clavulanic Acid.

Acute localized exanthematous pustulosis (ALEP) is a localized form of acute generalized exanthematous pustulosis, characterized by acute onset of multiple nonfollicular, pinhead-sized, sterile pustules following drug administration. Antibiotics, especially ß-lactams and macrolides, have been implicated in the majority of cases, although eruption after nonsteroidal antiinflammatory drugs and many other medications has also been reported. Skin reaction arises quickly within a few hours, resolving rapidly within a few days without treatment, and it is usually accompanied by fever and neutrophilic leukocytosis. We report herein all cases of ALEP described in literature, adding the case of a 35-year-old woman admitted to our hospital with outbreak of erythematous pustules on her face, neck, and chest after amoxicillin-clavulanic acid treatment.

Biologics that inhibit the Th17 pathway and related cytokines to treat inflammatory disorders.

INTRODUCTION: Advances in the understanding of TNF-α and IL-17 synergistic functions have recently led to the concept that patients who do not respond or who respond inadequately to TNF-α inhibitors may have IL-17-driven diseases, opening up the way for a new class of therapeutic development: Th17-inhibitors. Areas covered: In this review, the authors discuss the central role that the IL-23/Th17 axis plays in the pathogenesis of several inflammatory diseases, such as psoriasis, highlighting its position as a relevant therapeutic target. In particular, the authors start by giving a brief historical excursus on biologic agent development up until the success of TNF-α inhibitors, and continue with an overview of IL12/23 pathway inhibition. Next, they describe Th17 cell biology, focusing on the role of IL-17 in host defense and in human immune-inflammatory diseases, discussing the use and side effects of IL-17 inhibitors. Expert opinion: The IL-23/Th17 signaling pathway plays a central role in the pathogenesis of several inflammatory diseases, such as psoriasis. Recent data has demonstrated that biologics neutralizing IL-17 (ixekizumab, secukinumab) or its receptor (brodalumab) are highly effective with a positive safety profile in treating moderate to severe psoriasis, offering new treatment possibilities, especially for patients who do not respond adequately to anti-TNF-α therapies.

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.

Systemic Treatment of Adult Atopic Dermatitis: A Review.

Atopic dermatitis (AD) is a common chronic inflammatory skin disease that predominantly affects children. However, it can persist in adulthood and/or start at older ages. Due to its chronic nature and frequently occurring relapses, AD has a substantial effect on patients' quality of life, often requiring long-term systemic treatment, especially in adult patients, who are more frequently refractory to adequate topical treatment with mid- to high-potent corticosteroids and/or calcineurin inhibitors. Therefore, treatment with systemic therapies is often needed to take control of the disease, prevent exacerbations and improve quality of life. However, data regarding systemic treatment effectiveness and long-term safety in adult patients with AD are insufficient. Indeed, standardized international guidelines are lacking, and the treatment approach widely differs among diverse countries. This review focuses on the use of systemic treatments in adult AD patients analyzing published literature.

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.

Crosstalk between skin inflammation and adipose tissue-derived products: pathogenic evidence linking psoriasis to increased adiposity.

INTRODUCTION: Psoriasis is a chronic skin disorder associated with several comorbid conditions. In psoriasis pathogenesis, the role of some cytokines, including TNF-α and IL-17, has been elucidated. Beside their pro-inflammatory activity, they may also affect glucose and lipid metabolism, possibly promoting insulin resistance and obesity. On the other hand, adipose tissue, secreting adipokines such as chemerin, visfatin, leptin, and adiponectin, not only regulates glucose and lipid metabolism, and endothelial cell function regulation, but it may contribute to inflammation. Areas covered: This review provides an updated 'state-of-the-art' about the reciprocal contribution of a small subset of conventional cytokines and adipokines involved in chronic inflammatory pathways, upregulated in both psoriasis and increased adiposity. A systematic search was conducted using the PubMed Medline database for primary articles. Expert commentary: Because psoriasis is associated with increased adiposity, it would be important to define the contribution of chronic skin inflammation to the onset of obesity and vice versa. Clarifying the pathogenic mechanism underlying this association, a therapeutic strategy having favorable effects on both psoriasis and increased adiposity could be identified.