[Show abstract][Hide abstract] ABSTRACT: Backgrounddata on epidemiological impact and clinical characteristics of chronic hand eczema in Southern Europe are lacking.Objectivesto estimate prevalence of chronic hand eczema and its different stages of severity and refractoriness to standard therapy among patients accessing Italian dermatological reference centers, and to evaluate socio-demographic and clinical factors associated with each different stage.MethodsA cross-sectional multicenter study was conducted. Adult hand eczema patients, consecutively accessing 14 centers through a 6-month period, were enrolled. Patients were classified according to disease duration, severity and response to standard therapy with potent topical corticosteroids. Logistic regression analyses were performed to investigate relationship between socio-demographic and clinical data with different stages of eczema.Results981 patients participated. Hand eczema was chronic in 83.5% of patients. Among them, 21.3% were severe, 62% of these patients being refractory to standard therapy. Food processing and related works, health professions, craft and related trades works (builders, plumbers, electricians), hairdressers/beauticians and handicraft works were the jobs most frequently associated with having chronic hand eczema. Severe chronic hand eczema was more likely to be among men, older patients and those with lower education. Severe and refractory hand eczema was also more likely among unemployed and patients with allergic rhinitis and/or atopic dermatitis.Conclusions
Chronic hand eczema is frequent among hand eczema patients accessing dermatology centers. Many patients were severe and refractory to standard therapy. The appropriate identification of hand eczema is a first step necessary to implement effective and efficient treatments.This article is protected by copyright. All rights reserved.
British Journal of Dermatology 06/2014; · 3.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abstract Chronic inflammatory diseases represent a heterogeneous group of conditions that can affect practically any organ or system. An increasing number of biologic agents have been developed to selectively target the cell populations and signaling pathways involved in chronic inflammation, including cytokines, monoclonal antibodies and engineered receptors. This approach has been remarkably successful in alleviating some of the signs and symptoms of refractory autoimmune diseases. The use of this therapeutic strategy is likely to increase with the introduction of biosimilar agents. The different nature of these biological products makes the comparison of their pharmaceutical and clinical characteristics difficult, including safety and potency and these issues may be particularly relevant in the case of biosimilars. In addition, the heterogeneity of autoimmune diseases and of autoimmune patients, further adds to the complexity of choosing the right drug for each patient and predicting efficacy and safety of the treatment. In this review, we summarize actual knowledge about current biological agents and their use in autoimmune diseases, with a special emphasis for rheumatoid arthritis, inflammatory bowel diseases and psoriasis. The purpose of this analysis is to address the most critical issues raised by the rapid advancements in this field over recent years, and to acknowledge the potentially valuable gains brought about by the increasing availability of these new biologic agents.
[Show abstract][Hide abstract] ABSTRACT: The ingestion of nickel (Ni)-rich foods may result in allergic contact mucositis (ACM), a not yet well defined condition identifiable by oral mucosa patch test (omPT). Our aim was to characterize immunologically the ACM taking advantage from the allergen exposure that occurs during the omPT for Ni.
Thirty-seven symptomatic patients underwent to omPT for Ni. Before and after omPT, serum and urine Ni concentrations were determined by mass spectrometry, the white blood cells were counted by hemochromocytometric assay, the peripheral lymphocyte typing was carried out by flow cytometry, total IgE and cytokine serum concentrations were measured by immunoenzymatic assays. The local lymphocyte typing was performed by immunohistochemistry only after omPT.
According to the omPT outcomes, 25 patients were defined as Ni-sensitive and the remaining 12 as controls. After omPT, serum and urine Ni concentrations increased significantly in all patients, while a significant increment of circulating lymphocytes and neutrophils was highlighted, respectively, in Ni-sensitive and control patients. Consistently, the Th and Tc circulating lymphocytes, as well as the Th/Tc ratio increased significantly in Ni-sensitive patients after omPT. No noteworthy increment in serum concentrations of total IgE and selected cytokines was observed in any patient after omPT. The presence of CD3+, CD4+, and CD8+ cells was highlighted on the oral mucosa biopsy samples taken from Ni-sensitive patients after omPT.
In patients with ACM, a local adaptive response with increased lymphocyte trafficking appears to be the most likely mechanism of reaction to Ni administered with the omPT.
[Show abstract][Hide abstract] ABSTRACT: The complexity of the medical diagnosis is faced by practitioners relying mainly on their experiences. This can be acquired during daily practices and on-the-job training. Given the complexity and extensiveness of the subject, supporting tools that include knowledge extracted by highly specialized practitioners can be valuable. In the present work, a Decision Support System (DSS) for hand dermatology was developed based on data coming from a Visit Report Form (VRF). Using a Bayesian approach and factors significance difference over the population average for the case, we demonstrated the potentiality of creating an enhanced VRF that include a diagnoses distribution probability based on the DSS rules applied for the specific patient situation.
Studies in health technology and informatics 01/2014; 205:58-62.
[Show abstract][Hide abstract] ABSTRACT: Background: This is the first randomized, double-blind, placebo-controlled trial (EUDRACT No. 2009-013923-43) evaluating nickel oral hyposensitizing treatment (NiOHT) in patients with "systemic nickel allergy syndrome" (SNAS), characterized by Ni-allergic contact dermatitis and systemic reactions after eating Ni-rich food. Methods: Adults with positive Ni-patch test, who reported symptoms suggesting SNAS, which improved after Ni-poor diet, and were positive to Ni-oral challenge were eligible. Patients were randomly assigned to three treatments (1.5 μg, 0.3 μg, or 30 ng Ni/week) or placebo for a year, with progressive reintroduction of Ni-rich foods form the 5(th) month. Out of 141 patients randomized, 113 completed the trial. Endpoints were efficacy and tolerability of treatment. Results: During Ni-rich food re-introduction, the 1.5 μg Ni/week group had a mean VAS score significantly higher than placebo (p = 0.044), with significant improvement of gastrointestinal symptoms (p = 0.016;) and significantly fewer rescue medications. Cutaneous manifestations also improved but without reaching statistical significance. After the treatment, oral challenge with higher Ni doses than at baseline were needed to cause symptoms to flare-up in significantly more patients given 1.5 μg Ni/week than placebo (p = 0.05). Patients reported no side-effects. Conclusions: NiOHT is effective in SNAS, in particular on gastrointestinal manifestations, with trend toward improvement of cutaneous symptoms.
[Show abstract][Hide abstract] ABSTRACT: Little is known about the socio-economic burden of severe chronic hand eczema in patients refractory to treatment with potent corticosteroids.
To estimate the socio-economic burden of severe chronic hand eczema refractory to potent topical corticosteroids, and to establish an algorithm for the estimation of the health-related quality of life EuroQol five-dimensional (EQ-5D) utility index from the Dermatology Life Quality Index (DLQI) summary score.
A multicentre cost of illness study was conducted, adopting the societal perspective. Adult patients with severe and refractory chronic hand eczema were enrolled. Direct (e.g. drug treatment and travel) and indirect (i.e. loss of productivity) mean costs/patient-month were estimated. Health-related quality of life was assessed with the EQ-5D and DLQI questionnaires. An ordinary least square regression model was used to investigate relationships between health-related quality of life scores.
One hundred and four valid patients (mean age 44.5 years, 39.4% male) participated. Overall mean costs were €418.3/patient-month: loss of productivity contributed 43.7%, followed by hospitalization (16.1%) and travel (10.3%). Health-related quality of life scores were, on average, 0.50 (EQ-5D utility) and 11.3 (DLQI). Utility and DLQI summary were significantly related to each other.
Wellbeing and loss of productivity are the most important consequences in these patients. Appropriate treatment is necessary to improve patient health and productivity, which will contribute to reducing societal costs.
[Show abstract][Hide abstract] ABSTRACT: The complexity of the medical diagnostic practices is faced nowadays mainly with an extensive and long education and with on-the-job training for GPs. Despite these efforts, a big part of the diagnostic process remains implicit in the everyday practicies of skilled professionals. This project aims at an explicit tracking of this ability through the filling-in of an additional importance level for the voices in the Electronic Medical Record. The collected data leads to the extraction of rules that can empower a Decision Support System for hand dermatological practictioner with suggestios and/or diagnoses distribution probability for a specific situation.
Digital Human Modeling and Applications in Health, Safety, Ergonomics, and Risk Management. Healthcare and Safety of the Environment and Transport, Edited by Duffy, VincentG, 01/2013: pages 248-257; Springer Berlin Heidelberg., ISBN: 9783642391729
[Show abstract][Hide abstract] ABSTRACT: Calcipotriol, a vitamin D analogue, and betamethasone dipropionate, a high potency corticosteroid, are complementary agents for the topical treatment of psoriasis vulgaris. Robust evidence on the efficacy and safety of their fixed combination has been provided by randomized, double-blind, controlled clinical trials involving more than 7000 patients with the ointment formulation in psoriasis of the body and more than 4000 patients with the gel formulation in scalp psoriasis. These trials have shown that the fixed combination ointment is more effective and better tolerated, not only than placebo, but also than calcipotriol and tacalcitol monotherapies. In addition, it has proved, in most instances, to be more effective than betamethasone and at least as well tolerated. The same applies to the gel for scalp and body psoriasis. Safety studies have excluded that repeated courses of treatment with the fixed combination for up to one year produce systemic effects. Studies have also shown that the fixed combination treatment improves quality of life to a significantly greater extent than calcipotriol, with the once daily regimen most appreciated by patients, in both active disease and recurrency. Because of the extensive evidence, American and European guidelines recommend the calcipotriol/betamethasone dipropionate fixed combination as first line topical treatment for mild to moderate plaque psoriasis of the body and scalp.
Giornale Italiano di Dermatologia e Venereologia 12/2012; 147(6):609-624. · 0.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Epidermolysis bullosa acquisita (EBA) is a rare autoimmune mucocutaneous bullous disease caused by autoantibodies against type VII collagen, a component of anchoring fibrils which stabilizes the dermo-epidermal adherence. Type VII collagen is composed of a collagenous domain linked by non-collagenous NC1 and NC2 domains. Objective: To assess the repeatability, sensitivity and specificity of a recently developed ELISA for detection of autoantibodies anti-type VII collagen and to ascertain whether it may be a marker of disease activity in EBA. Patients and Methods: Using this ELISA able to recognize autoantibodies against NC1 and NC2 epitopes of type VII collagen, we tested 14 EBA sera, 30 healthy control sera and 113 disease control sera. Results: Twelve out of the 14 EBA sera were positive in ELISA, with autoantibody titers varying from 7.2 to 127.9 U/ml (cut-off value: <6), the sensitivity of the method being of 85.7%. Among the controls, only two bullous pemphigoid sera resulted positive, the specificity being of 98.6%. A good correlation was found between EBA disease severity expressed as ABSIS score and the serum levels of anti-collagen VII autoantibodies measured by ELISA (n=14; r=0.965; p=0.0001). The intra- and inter-assay coefficients of variation of the ELISA method ranged from 6.3% to 18.3%. Conclusions: This NC1 + NC2 ELISA can be a practical assay for the diagnosis of EBA. The correlation between autoantibody titers and disease severity suggests its usefulness as a marker of disease activity in EBA, which however should be confirmed by studies on larger series of patients.
British Journal of Dermatology 08/2012; · 3.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Psoriasis vulgaris (PsV) and psoriatic arthritis (PSA) are inter-related heritable inflammatory skin diseases. Psoriatic lesions develop as a result of abnormal immune responses, hyperproliferation and altered differentiation of keratinocytes, and a notable subset of psoriatic patients develops PsA, characterized by joints inflammation. Recently, biological drugs were introduced to treat these diseases. However, this therapy has already been associated with the development of serious life-threatening infections, such as the reactivation of human polyomavirus JC (JCV), responsible for the progressive multifocal leukoencephalopathy (PML), a lethal demyelinating disease caused by oligodendrocytes lytic infection. Therefore, the aims of our study were the investigation of the possible JCV reactivation in PsV and PsA patients treated with adalimumab, etanercept, and methotrexate, performing quantitative real-time PCR in sera and skin biopsies at the time of recruitment (T0) and after 3 (T3) and 6 (T6) months of treatment, and the sequencing analysis of the JCV non-coding control region (NCCR). We found JCV DNA in 5/15 PsV patients and in 2/15 PsA patients and JCV NCCR sequence analysis always showed a structure similar to non-pathogenic CY archetype, with random occurrence of a few irrelevant point mutations. Nevertheless the poor number of patients analyzed, our preliminary data can pave the way for taking into account that the follow-up of JCV DNA detection and the JCV NCCR sequence analysis in psoriatic patients may be important to evaluate the risk of PML onset, considering that patients affected by autoimmune diseases and treated with biologics continue to rise.
Journal of Cellular Physiology 03/2012; 227(12):3796-802. · 4.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Rituximab induces depletion of B cells and has shown efficacy in antibody-mediated autoimmune disorders. In studies on small series of patients with pemphigus, rituximab administration results in significant improvement. However, differences in inclusion criteria, treatment protocols, and follow-up make it difficult to derive uniform conclusions.
We sought to test the efficacy and tolerability of rituximab as adjuvant therapy to corticosteroids in the treatment of pemphigus.
In all, 42 patients with pemphigus were treated with rituximab and followed up for up to 5 years. No additional immunosuppressive agents were used. Steroids were rapidly tapered. Outcomes were the proportion of patients who achieved a complete response on or off therapy, the rate of discontinuation of corticosteroid within 6 months, length of remission, time to relapses, and occurrence of adverse events.
In all, 36 of 42 patients (86%; 95% confidence interval 75%-96%) achieved a complete response on or off therapy and discontinued steroids within 6 months from induction therapy. Six patients had a complete response off therapy with an additional infusion of rituximab 6 months after initial treatment. Twenty patients experienced a total of 34 relapses; the time to relapse was 8 to 64 months. Every relapse was treated with rituximab (500 mg) without corticosteroids, which induced a new complete response. No serious adverse events were observed.
Lack of a control group is a limitation.
Rituximab therapy induces prolonged clinical remission in patients with pemphigus. Coadministration of other immunosuppressive agents is not necessary. Relapses can be managed with additional infusions administered on demand.
Journal of the American Academy of Dermatology 01/2012; 67(4):617-22. · 4.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Nickel contact allergy remains common in Western countries, and the dermatitis may require prolonged treatment. The development of new strategies aimed at improving the quality of life of affected individuals is needed.
To investigate the efficacy of oral hyposensitization in nickel-allergic individuals and how this affects in vitro T cell responsiveness to the metal.
Twenty-eight nickel-allergic patients received a daily dose of 50 µg of elemental nickel (given as NiSO(4) ·6H(2) O) in cellulose capsules for 3 months. Severity of clinical manifestations, in vivo nickel responsiveness and in vitro T cell responses to the metal were assessed after 1 and 3 months.
Twenty-six patients finished the study. In these patients, oral hyposensitization ameliorated clinical manifestations despite continued nickel exposures, and increased the threshold of skin responsiveness to nickel. The 12 enrolled patients in the immunological study showed decreased in vitro T lymphocyte responsiveness to the metal, in terms of both cell proliferation and cytokine release. In the 1-year follow-up, 50% of the patients experienced relapses of the clinical manifestations at sites of topical exposure to nickel.
Our study suggested therapeutic efficacy of oral hyposensitization in allergic individuals. Placebo-controlled studies are required to confirm the results and determine the optimal therapeutic regimen for prolonged beneficial effects.
[Show abstract][Hide abstract] ABSTRACT: Toll-like receptors (TLRs) are a key part of the innate immune system that detect pathogen-associated molecular patterns (PAMPs) of microorganisms and their stimulation results in the activation of signaling pathways leading to the modulation of inflammatory and immune responses. Since psoriasis is a complex, inflammatory and immune skin disease, characterized by an abnormal immune response and increased proliferation of keratinocytes, with an increased production of proinflammatory cytokines, TLRs could play an important role in the pathogenesis of the disease. We propose to assess the modulation of TLR expression on psoriatic skin of patients treated with Adalimumab and systemic conventional therapies. We therefore recruited fifteen patients: ten were treated with adalimumab and five with systemic conventional therapies; their clinical conditions were analyzed by PASI index and skin biopsies were evaluated for TLR1 and TLR2 expression by immunohistochemistry assays. Our data suggest adalimumab is not only able to improve the clinical condition of psoriatic patients, but also to modulate TLR1 and TLR2 expression involved in psoriasis, as in healthy skin. Adalimumab is a most promising biological drug able to orchestrate immune and inflammatory responses in psoriatic lesions, recovering TLR expression on basal keratinocytes and improving clinical conditions of psoriatic patients, with no evident side effects.
International journal of immunopathology and pharmacology 01/2011; 24(1):185-8. · 2.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Lupus nephritis (LN) may represent a diagnostic problem, particularly in pediatric patients that present with typical histological lesions but do not fulfill the American Rheumatism Association (ARA) criteria for the diagnosis of systemic lupus erythematosus (SLE). Based on the well-described deposition of immunoglobulins (Ig) and complement at the dermoepithelial junction in SLE, we hypothesized that skin biopsies may help in the diagnosis of LN. To test this hypothesis, we carried out a pilot study, performing a skin biopsy in 22 patients with LN and 13 patients with lupus-like lesions, regardless of the time elapsed from onset of renal disease. The latter group of patients was further divided into a purely renal group, designated as isolated full-house nephropathy (FHN), and a dubious cases group, presenting with additional clinical and biological features consistent with SLE but insufficient for diagnosing SLE. None of the 6 isolated FHN patients had positive skin immunofluorescence. Conversely, 5/7 patients in the dubious cases group (p<0.02) and 13/22 in the LN group (p<0.002) had positive staining for C1q, and 5/7 patients in the dubious cases group (p<0.02) and 16/22 patients in the LN group (p<0.001) had positive staining for IgM. No correlation was observed with the time elapsed from the initial diagnosis. These data suggest that skin biopsies may help distinguishing LN from isolated FHN. In addition, they identify an intermediate group of patients with evidence of systemic involvement despite the absence of a sufficient number of ARA criteria to be labeled as SLE.
[Show abstract][Hide abstract] ABSTRACT: Pemphigus vulgaris (PV) is a severe autoimmune bullous skin disease and is primarily associated with IgG against desmoglein 3 (dsg3), a desmosomal adhesion protein. In light of the recent association of autoreactive T helper (Th) 2 cells with active PV, the present study sought to relate the occurrence of Th2-regulated dsg3-specific autoantibody subtypes, i.e. IgE and IgG4, in 93 well-characterized PV patients. Patients with acute onset PV (n=37) showed the highest concentrations of serum IgE and IgG4 autoantibodies, which were significantly lower in PV patients in remission (n=14). Furthermore, there was a strong correlation between dsg3-reactive IgE and IgG4 in acute onset, but not in chronic active (n=42) or remittent patients. Additionally, intercellular IgE deposits were detected in the epidermis of acute onset PV. Thus, dsg3-specific IgE and IgG4 autoantibodies are related to acute onset disease which provides additional support to the concept that PV is a Th2-driven autoimmune disorder.
[Show abstract][Hide abstract] ABSTRACT: The basophil activation test (BAT) has been recently described as a useful in vitro tool for diagnosis of allergy to Anisakis species in patients with acute urticaria.
To evaluate the relationship between sensitization to Anisakis simplex and chronic urticaria (CU), using flow cytometry analysis of in vitro BAT. Methods. A. simplex sensitization was evaluated in patients with CU (n = 57) and in atopic (n = 22) and healthy controls (n = 20) by means of skin prick test (SPT), specific IgE and Anisakis-induced BAT using a triple-labelled strategy with anti-CD123, anti-human leucocyte antigen DR and anti-CD63 antibodies. During a follow-up period of 6 months in 10 patients with CU who accepted a fish-free dietary regimen, the diagnostic performance of the in vivo and in vitro methods was calculated, and changes in specific IgE and BAT were evaluated with respect to clinical response.
A significant association between CU and A. simplex sensitization was found, with an overall prevalence of 75.4% in patients with CU (43/57) compared with 18% (4/22) and 10% (2/20) of the atopic and healthy controls, respectively (P < 0.0001). BAT (cut-off > 13%) had the highest sensitivity and specificity, with significantly better ability than specific IgE testing for the identification of A. simplex sensitization in patients with CU. During the 6-month follow-up, clinical improvement was seen in all patients, and specific IgE and BAT results decreased to normal values in 6/10 (60%) and 10/10 (100%) patients, respectively.
BAT can be considered a reliable new in vitro method to evaluate A. simplex hypersensitivity in patients with CU, supplementing standardized procedures in both diagnosis and follow-up.
Clinical and Experimental Dermatology 10/2009; 35(7):765-70. · 1.33 Impact Factor