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Cugno M.,University of Milan | Asero R.,Ambulatorio di Allergologia | Tedeschi A.,Unita Operativa di Allergologia e Immunologia Clinica | Lazzari R.,Unita Operativa di Dermatologia | Marzano A.V.,Unita Operativa di Dermatologia
Current Vascular Pharmacology | Year: 2012

Urticaria is a skin disease characterised by short-lived surface swellings of the dermis (wheals) frequently accompanied by itching. It is classified as acute or chronic depending on whether the wheal recurrence occurs for less or more than six weeks. Acute urticaria is often due to a hypersensitivity reaction, whereas about 50% of the cases of chronic urticaria are regarded as autoimmune. Urticaria may occur alone or in association with a deeper swelling (angioedema) involving the subcutaneous and/or submucosal tissues, and last from hours to a few days. Angioedema can also develop alone, and may be idiopathic or be caused by allergies, inherited or acquired deficiencies of C1-inhibitor protein, or adverse drug reactions. An interplay between inflammation and coagulation has been proposed as a pathomechanism in urticaria and urticaria-associated angioedema (in which histamine and thrombin are involved), as well as in angioedema due to C1-inhibitor deficiency, which involves various biological systems. An increase in the plasma markers of thrombin generation, fibrinolysis and inflammation has been documented during exacerbations of urticaria and angioedema, with the marker levels decreasing to normal during remission. However, the hypercoagulable state in chronic urticaria and angioedema has not been reported to be associated with any increased risk of thrombosis, although there have been a number of reports of cardiovascular events occurring during episodes of acute urticaria. These observations have provided the rationale for the clinical evaluation of anticoagulant and antifibrinolytic drugs, the efficacy of which has sometimes been demonstrated. © 2012 Bentham Science Publishers.


Cugno M.,University of Milan | Marzano A.V.,Unita Operativa di Dermatologia | Lorini M.,University of Milan | Carbonelli V.,University of Milan | Tedeschi A.,Unita Operativa di Allergologia e Immunologia Clinica
PLoS ONE | Year: 2014

Thrombotic risk is increased in eosinophil-mediated disorders, and several hypotheses have been proposed to link eosinophilia and thrombosis. In particular, eosinophils have been described as source of tissue factor (TF), the main initiator of blood coagulation; however, this aspect is still controversial. This study was aimed to evaluate whether TF expression varies in eosinophils isolated from normal subjects and patients with different hypereosinophilic conditions. Eosinophils were immunologically purified from peripheral blood samples of 9 patients with different hypereosinophilic conditions and 9 normal subjects. Western blot analysis and real-time polymerase chain reaction (RT-PCR) were performed to test eosinophil TF expression. For comparison, TF expression was evaluated in monocytes from blood donors and in human endothelial (ECV304) and fibroblast (IMR90) cell lines. Western blot analysis revealed a major band of 47,000 corresponding to native TF in homogenates of purified eosinophils with a higher intensity in the 9 patients than in the 9 controls (p< 0.0001). According to RT-PCR cycle threshold (Ct), TF gene expression was higher in eosinophils from patients than in those from controls, median (range) 35.10 (19.45-36.50) vs 37.17 (35.33-37.87) (p= 0.002), and was particularly abundant in one patient with idiopathic hypereosinophilic syndrome and ischemic heart attacks (Ct: 19.45). TF gene expression was moderate in monocytes, Ct: 31.32 (29.82-33.49) and abundant in endothelial cells, Ct: 28.70 (27.79-29.57) and fibroblasts, Ct: 22.77 (19.22-25.05). Our results indicate that human blood eosinophils contain variable amounts of TF. The higher TF expression in patients with hypereosinophilic disorders may contribute to increase the thrombotic risk. © 2014 Cugno et al.


Amerio P.,University of Chieti Pescara | Amoruso G.,University of Catanzaro | Bardazzi F.,Ospedale S.Orsola Malpighi | Campanati A.,Marche Polytechnic University | And 10 more authors.
Journal of Dermatological Treatment | Year: 2013

The biologic agents can be highly efficacious in the treatment of psoriasis and psoriatic arthritis; however, their use is associated with an increased risk of developing active TB. In particular, TNF-α plays critical role in preventing TB infection and reactivation of latent TB infection (LTBI). Therefore, it is critical that all patients be screened for LTBI prior to initiating therapy. An expert panel of Italian dermatologists met recently with the goal of producing a consensus paper on screening and chemoprophylaxis for LTBI in Italian psoriasis patients treated with biologics. Current recommendations for the screening algorithm include medical history, chest x-ray, and tests that evaluate immunologic response to the presence of Mycobacterium tuberculosis. Patients with positive screening results and without active disease are to be treated with a full course of chemoprophylaxis; however, if the patient is compliant and tolerating the regimen, biologic therapy for psoriasis may be started after at least 1 month on prophylactic therapy when prompt control of disease is required. © 2013 Informa Healthcare USA on behalf of Informa UK Ltd.


Tedeschi A.,Unita Operativa di Allergologia e Immunologia Clinica | Marzano A.V.,Unita Operativa di Dermatologia | Lorini M.,Unita Operativa di Allergologia e Immunologia Clinica | Lorini M.,University of Milan | And 2 more authors.
Journal of the European Academy of Dermatology and Venereology | Year: 2015

Background Bullous pemphigoid (BP) is an autoimmune blistering disease due to autoantibodies against two hemidesmosomal antigens, namely BP180 and BP230, and characterized by coagulation activation both at cutaneous and systemic levels. Skin-infiltrating eosinophils contribute to bulla formation and, upon activation, are supposed to initiate the coagulation cascade. Objective The aim of this study was to investigate whether the activation of eosinophils and coagulation are linked in BP. Methods We evaluated the correlation between eosinophil cationic protein (ECP) levels and concentrations of the prothrombotic markers F1 + 2 and D-dimer in blister fluid and blood samples of 30 BP patients. Thirty healthy subjects were used as normal controls. Results ECP, F1 + 2 and D-dimer plasma levels were significantly higher in BP patients than in normal subjects. A significant correlation was found between ECP plasma levels and blood eosinophil count (r = 0.54, P = 0.002). F1 + 2 plasma levels positively correlated with disease severity, expressed as the percentage of body surface area involved (r = 0.36, P = 0.048). A striking increase in ECP (288.8 ± 45.2 ng/mL), F1 + 2 (31 409.9 ± 2929.4 pmol/L) and D-dimer levels (342 798.3 ± 44 206 ng/mL) was found in blister fluid from BP patients. In blister fluid, ECP levels were significantly higher than in peripheral blood (P < 0.0001) and were positively correlated with the levels of both F1 + 2 (r = 0.4, P = 0.02) and D-dimer (r = 0.5, P = 0.0045). Conclusions ECP levels are strikingly elevated in blister fluids from BP patients and correlate with markers of coagulation activation, supporting the view that eosinophils initiate the coagulation cascade at skin level. © 2014 European Academy of Dermatology and Venereology.


PubMed | Unita Operativa di Dermatologia, Unita Operativa di Allergologia e Immunologia Clinica and University of Milan
Type: Journal Article | Journal: PloS one | Year: 2014

Thrombotic risk is increased in eosinophil-mediated disorders, and several hypotheses have been proposed to link eosinophilia and thrombosis. In particular, eosinophils have been described as source of tissue factor (TF), the main initiator of blood coagulation; however, this aspect is still controversial. This study was aimed to evaluate whether TF expression varies in eosinophils isolated from normal subjects and patients with different hypereosinophilic conditions. Eosinophils were immunologically purified from peripheral blood samples of 9 patients with different hypereosinophilic conditions and 9 normal subjects. Western blot analysis and real-time polymerase chain reaction (RT-PCR) were performed to test eosinophil TF expression. For comparison, TF expression was evaluated in monocytes from blood donors and in human endothelial (ECV304) and fibroblast (IMR90) cell lines. Western blot analysis revealed a major band of 47,000 corresponding to native TF in homogenates of purified eosinophils with a higher intensity in the 9 patients than in the 9 controls (p<0.0001). According to RT-PCR cycle threshold (Ct), TF gene expression was higher in eosinophils from patients than in those from controls, median (range) 35.10 (19.45-36.50) vs 37.17 (35.33-37.87) (p=0.002), and was particularly abundant in one patient with idiopathic hypereosinophilic syndrome and ischemic heart attacks (Ct: 19.45). TF gene expression was moderate in monocytes, Ct: 31.32 (29.82-33.49) and abundant in endothelial cells, Ct: 28.70 (27.79-29.57) and fibroblasts, Ct: 22.77 (19.22-25.05). Our results indicate that human blood eosinophils contain variable amounts of TF. The higher TF expression in patients with hypereosinophilic disorders may contribute to increase the thrombotic risk.


Pradella L.M.,University of Bologna | Zuntini R.,University of Bologna | Magini P.,University of Bologna | Ceccarelli C.,Unita Operativa di Anatomia Patologica | And 5 more authors.
Journal of Medical Genetics | Year: 2011

Background: Cowden syndrome (CS) is an autosomal dominant disorder characterised y macrocephaly, specific mucocutaneous features and predisposition to benign and malignant tumours. Detectable mutations in the PTEN gene account for 80-85% of cases. Methods/Results: Here, the authors report a patient with macrocephaly and typical CS mucocutaneous features who developed dysplastic cerebellar gangliocytoma and two synchronous thyroid cancers of papillary and oncocytic type, in whom a germline 500-Kb deletion on chromosome 10q23 including PTEN was detected. Molecular characterisation of thyroid cancer led to the identification of the oncogenic BRAFV600E mutation in the papillary carcinoma. BRAFV600E has been proposed to cause cancer only in the presence of a tumour-suppressor mutation, which, in this case, could be the PTEN deletion. In the oncocytic carcinoma, a large deletion in the mitochondrial-DNA-encoded MTND1 was found, associated with respiratory complex I disassembly, which was subsequently shown to be a constitutional, de novo genetic lesion. Conclusions: This is the first reported case of a patient with CS carrying constitutional deletions in both the nuclear and the mitochondrial genome that might help elucidate some aspects of CS pathogenesis.


Veraldi S.,University of Milan | Bottini S.,Unita Operativa di Dermatologia | Rizzitelli G.,Fondazione Don Carlo Gnocchi | Persico M.C.,University of Milan
Journal of Dermatological Treatment | Year: 2012

We evaluated retrospectively the efficacy and tolerability of oral albendazole (400 mg/day for 1 week) in 78 patients with hookworm-related cutaneous larva migrans characterized by multiple and/or extensive lesions. The diagnosis was based on history and the clinical picture. Neither topical or systemic drugs nor physical treatments were used. All patients were followed-up for at least 3 months after the therapy. All patients were cured at the end of the therapy. The disappearance of pruritus was reported after 23 days and skin lesions after 57 days of therapy. One patient reported nausea and abdominal pain; another patient reported worsening of pruritus: in both cases it was not necessary to stop the therapy. No recurrences were observed during follow-up. One week of therapy with 400 mg/day oral albendazole is very effective (cure rate: 100%) in patients with cutaneous larva migrans characterized by multiple and/or extensive lesions. This therapeutical regimen is not accompanied by the appearance of new and/or more severe side effects. © 2012 Informa Healthcare USA on behalf of Informa UK Ltd.


Marzano A.V.,Unita Operativa di Dermatologia | Trevisan V.,Unita Operativa di Dermatologia | Eller-Vainicher C.,Unita Operativa di Endocrinologia e Diabetologia | Cairoli E.,Unita Operativa di Endocrinologia e Diabetologia | And 5 more authors.
British Journal of Dermatology | Year: 2012

Background Vitamin D deficiency plays a role in autoimmune diseases and risk of fractures. No data are available on vitamin D levels and vertebral fractures in autoimmune bullous skin diseases. Objectives To assess serum vitamin D levels and the prevalence of vertebral fractures in patients with pemphigus vulgaris (PV) and bullous pemphigoid (BP), potentially fatal autoimmune bullous disorders. Methods We studied 13 consecutive inpatients with untreated active PV (six men and seven women, mean ± SD age 53·5 ± 14·3 years), 15 with BP (seven men and eight women, mean ± SD age 76·9 ± 12·4 years) and 28 age-, body mass index- and sex-matched controls. The 25-hydroxyvitamin D (25-OHD) levels and presence of vertebral fractures on spinal X-ray were assessed in all subjects. Results In patients with PV, 25-OHD levels were lower (mean ± SD 12 ± 4·4 ng mL-1) and prevalence of severe hypovitaminosis D higher (62%) than in controls (mean ± SD 22·2 ± 11·7 ng mL-1, P = 0·012; 23%, P = 0·0047, respectively). The prevalence of fractures was 54% and 31% in patients with PV and controls, respectively. Patients with BP showed lower 25-OHD levels (mean ± SD 9·6 ± 7·2 ng mL-1) and higher prevalence of severe hypovitaminosis D (73%) than controls (mean ± SD 22·6 ± 18·7 ng mL-1, P = 0·022; 27%, P = 0·01, respectively). The prevalence of fractures tended to be higher in patients with BP than in controls (67% vs. 33%, respectively, P = 0·068). Conclusions The low 25-OHD levels found in PV and BP may suggest a role for this agent in their pathogenesis. The increased prevalence of fractures should be taken into consideration in patients who must be given corticosteroids. © 2012 British Association of Dermatologists.


Savoia F.,Unita Operativa di Dermatologia | Gaddoni G.,Unita Operativa di Dermatologia | Patrizi A.,University of Bologna | Sgubbi P.,University of Bologna
Medico e Bambino | Year: 2012

The case of a 3-month-old boy that was visited because of a brownish, hyperkeratotic and slightly desquamative dermatitis of the inguinal folds, perineum and perianal area is reported. The patient was healthy, asymptomatic and the remaining physical examination was normal. Anamnesis revealed frequent and thorough washings of the diaper area with a synthetic pH acid detergent. A diagnosis of pigmented and hyperkeratotic napkin dermatitis was made. Complete healing was obtained within 5 days using a delicate detergent instead of the previous one and using a moisturizing cream containing omega 3 and omega 6 fatty acids. Pigmented and hyperkeratotic napkin dermatitis is a peculiar, under-reported type of irritant contact dermatitis that falls within differential diagnosis with many other dermatitis of the diaper area.


Cordova A.,University of Palermo | Toia F.,University of Palermo | la Mendola C.,University of Palermo | Orlando V.,University of Palermo | And 10 more authors.
PLoS ONE | Year: 2012

T lymphocytes are often induced naturally in melanoma patients and infiltrate tumors. Given that γδ T cells mediate antigen-specific killing of tumor cells, we studied the representation and the in vitro cytokine production and cytotoxic activity of tumor infiltrating γδ T cells from 74 patients with primary melanoma. We found that γδ T cells represent the major lymphocyte population infiltrating melanoma, and both Vδ1+ and Vδ2+ cells are involved. The majority of melanoma-infiltrating γδ cells showed effector memory and terminally-differentiated phenotypes and, accordingly, polyclonal γδ T cell lines obtained from tumor-infiltrating immune cells produced IFN-γ and TNF-α and were capable of killing melanoma cell lines in vitro. The cytotoxic capability of Vδ2 cell lines was further improved by pre-treatment of tumor target cells with zoledronate. Moreover, higher rate of γδ T cells isolation and percentages of Vδ2 cells correlate with early stage of development of melanoma and absence of metastasis. Altogether, our results suggest that a natural immune response mediated by γδ T lymphocytes may contribute to the immunosurveillance of melanoma. © 2012 Cordova et al.

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