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ABSTRACT: Tumor necrosis factor-α (TNF-α) inhibitors represent efficacious therapeutic agents in many chronic inflammatory diseases such as psoriasis and rheumatoid arthritis. However they have been connected with increased risk of infection and reactivation of a variety of infectious agents, such as viruses. The reactivation of varicella zoster virus infection causes herpes zoster (HZ), a self-limiting, dermatomally localized, vesicular rash that can be accompanied by postherpetic neuralgia and severe neurological complications.
Limited information has been published regarding HZ during therapy with TNF-α inhibitors especially for the occurrence of HZ during adalimumab treatment. We report the case of a 58-year-old immunocompetent man with a 18-year history of plaque psoriasis who develops ophthalmic HZ during treatment with adalimumab.
We report this case to enrich the literature and to highlight the increased risk of HZ infections in patient on anti-TNF-α therapy (incidence of HZ is about 3-fold increased respect to general population). Clinically, these infections often have atypical presentations that may hamper prompt diagnosis. Therefore, it is very important to identify early signs and symptoms of herpes zoster in patients on biologic therapy in order to start prompt efficient antiviral treatment to prevent the development of severe complications.
Journal of Dermatological Case Reports 03/2013; 7(1):1-4.
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ABSTRACT: Abstract Background: Monocyte Chemoattractant Protein-1 (MCP-1) is a chemokine locally and systemically augmented in psoriasis. A single nucleotide polymorphism in MCP-1 promoter region -2518A→G is associated with higher gene expression. Objective: To evaluate MCP-1 plasma level in psoriatic patients and to relate any association in plasmatic and cutaneous MCP-1 with clinical improvement due to biological drugs. Methods: Blood samples were obtained from: (i) 30 Caucasian patients with psoriasis and 10 controls, for determining MCP-1 plasma concentrations and -2518A→G polymorphism occurrence, (ii) 16 psoriatic patients treated by anti TNF-α Adalimumab/Etanercept or by anti CD-11 Efalizumab, before and after 2 months of treatment. Moreover, biopsies were performed on lesional skin of 5 patients treated by anti TNF-α. MCP-1 plasma concentration and cutaneous expression were determined by ELISA and qRT-PCR. Results: MCP-1 plasma level was significantly increased in psoriatic patients. A2518G polymorphism was similarly distributed in patients and controls and unrelated to MCP-1 plasma level or to PASI. All patients receiving biological drugs showed significant clinical improvement. Anti TNF-α therapy moderately reduced MCP-1 plasma concentration and robustly decremented MCP-1 expression in lesional skin. Conclusion: MCP-1 should be a potential local inflammatory marker in psoriatic patients to assess disease severity and anti TNF-α treatment efficacy.
Journal of Dermatological Treatment 03/2013; · 1.23 Impact Factor
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ABSTRACT: Interleukin (IL)-1 family comprise 11 members that play an important role in immune regulation and inflammatory process. Retinoids exert complex effects on the immune system, having anti-inflammatory effects in chronic dermatological diseases. Vitamin D (vitD) and analogs have been shown to suppress TNF-α-induced IL-1α in human keratinocytes (KCs). In the present study, we investigated IL-1 family members in psoriasis and the effects of vitD and retinoic acid (RA) on these members. We analyzed IL-1 family members gene expression in psoriatic skin and in ex vivo skin organ culture exposed to TNF-α, IL-17 or broadband UVB; afterwards, treatment with vitD or RA was performed and IL-1 family members mRNA was evaluated. Similarly, KCs were stimulated with IL-17 and subsequently treated with vitD. IL-1 family members were enhanced in psoriatic skin and in ex vivo skin organ cultures after pro-inflammatory stimuli (TNF-α, IL-17 and UVB). RA and vitD were able to suppress this enhancement.
Archives for Dermatological Research 02/2013; · 2.28 Impact Factor
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ABSTRACT: : Intracranial malignancies can be complicated by seizure activity, and anticonvulsants such as phenytoin are usually administered to prevent this neurological kind of complication. Cranial radiation therapy is instead the treatment of choice when the tumor is unresectable. Anyway, the combination of phenytoin and cranial radiation therapy can lead to a rare and severe mucocutaneous complication called EMPACT syndrome. It is composed of "erythema (E) multiforme (M) associated with phenytoin (P) and (A) cranial radiation (C) therapy (T)." Herein, we report 2 cases of EMPACT syndrome related to the use of phenobarbital instead of phenytoin as usually described in literature.
Dermatitis 01/2013; 24(1):37-9. · 1.21 Impact Factor
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ABSTRACT: 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.
Experimental Dermatology 11/2012; 21(11):892-4. · 3.54 Impact Factor
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ABSTRACT: : A wide spectrum of skin toxicities has been described in patients receiving epidermal growth factor receptor (EGFR), inhibitors, including papulopustular rash, xerosis and fissures, pruritus, mucositis, paronychia, and hair changes.Trichomegaly of the eyelashes is a rare adverse effect of EGFR inhibitor therapy and is characterized by a paradoxical overgrowth of eyelashes. We present 3 cases of trichomegaly occurred during EGFR inhibitor therapy.
Dermatitis 09/2012; 23(5):237-8. · 1.21 Impact Factor
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ABSTRACT: The trans-resveratrol (t-res), a non-flavonoid polyphenol extracted from different plants, has recently earned interest for application on the skin for different applications. In this work, the potential of nanocarriers, namely transfersomes and ethanol-containing vesicles, to deliver t-res into/through the skin was investigated. Thus, transfersomes with different surfactants, namely polysorbate 80 (Tw80), sodium cholate (SC) and sodium deossicholate (SDC) and ethanol-containing vesicles with different lipid composition, namely soy phosphatidylcholine (SPC) and cholesterol (chol), encapsulating t-res were prepared and characterized. The nanocarriers had a mean diameter ranging between 83 and 116nm with a high t-res encapsulation efficiency (≥70%). Moreover, cytotoxicity as well as the inhibition of production of reactive oxygen species (ROS) and lipid peroxidation, following incubation of H(2)O(2)-stimulated human keratinocyte (HaCaT) with t-res, as free or encapsulated into the nanocarriers, were investigated. Only blank nanocarriers containing Tw80 or ethanol were cytotoxic and led to increase of ROS, but this effect was not observed when using nanocarriers encapsulating t-res. Finally, permeation studies on porcine skin carried out on Franz diffusion cells, showed that only ethanol-containing vesicles based SPC were able to promote t-res permeation through the skin.
International journal of pharmaceutics 08/2012; · 2.96 Impact Factor
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Occupational and environmental medicine 06/2012; 69(10):772. · 3.64 Impact Factor
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ABSTRACT: Spontaneous protein deamidation of labile asparagines (Asn), generating abnormal isoaspartyl residues (IsoAsp), is associated with cell aging and enhanced by an oxidative microenvironment. The presence of isopeptide bonds impairs protein structure/function and can trigger autoimmune responses. To minimize the damage, IsoAsp can be "repaired" by a specific L-isoaspartate-(D-aspartate)-protein-O-methyltransferase. The condition of chronic oxidative stress reported in psoriatic patients, and the potential etiological role of unknown self-antigens, prompted us to investigate Asn deamidation in psoriatic tissues. Erythrocytes (RBC) were selected as the model system since, lacking protein synthesis apparatus, they are unable to replace damaged proteins. Blood samples were obtained from 36 patients and 34 controls. L-isoAsp content was highly increased in RBC membrane proteins from psoriatic patients. Deamidated species included ankyrin, band 4.1, band 4.2 and the integral membrane protein band 3. A functional analysis demonstrated that this result was unrelated to a reduced efficiency of the S-adenosylmethionine-dependent repair system suggesting an increased protein instability at Asn sites, responsible for IsoAsp accumulation in psoriatic patients.
Archives for Dermatological Research 05/2012; 304(6):475-9. · 2.28 Impact Factor
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Wolfgang Uter,
Werner Aberer,
José Carlos Armario-Hita,
José M Fernandez-Vozmediano, Fabio Ayala,
Anna Balato,
Andrea Bauer,
Barbara Ballmer-Weber,
Aiste Beliauskiene,
Anna Belloni Fortina, [......],
Thomas Rustemeyer,
Javier Sánchez-Pérez,
Jane E Sansom,
Juan Fco Silvestre,
Dagmar Simon,
Radoslaw Spiewak,
Barry N Statham,
Natalie Stone,
Mark Wilkinson,
Axel Schnuch
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ABSTRACT: 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.
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.
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.
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.
Contact Dermatitis 04/2012; 67(1):9-19. · 3.51 Impact Factor
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Indian journal of dermatology, venereology and leprology 03/2012; 78(2):228. · 0.98 Impact Factor
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02/2012; , ISBN: 978-953-307-878-6
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ABSTRACT: 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.
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.
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.
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.
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.
Immunopharmacology and Immunotoxicology 02/2012; 34(4):548-60. · 1.83 Impact Factor
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ABSTRACT: 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.
Clinical and Developmental Immunology 01/2012; 2012:747204. · 1.84 Impact Factor
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ABSTRACT: Improved diagnosis of psoriasis, by new biomarkers, is required for evaluating the progression rate of the disease and the response to treatment. Haptoglobin (Hpt), a glycoprotein secreted by hepatocytes and other types of cells including keratinocytes, was found with glycan changes in psoriasis and other diseases. We previously reported that Hpt isolated from plasma of psoriatic patients is more fucosylated than Hpt of healthy subjects. The aim of this study was to compare the glycosylation pattern of Hpt isolated from skin scales or plasma of patients with psoriasis with that of Hpt from cornified epidermal layer or plasma of healthy subjects. High performance liquid chromatography analysis of the glycans isolated from the protein backbone revealed that glycan patterns from skin and plasma of patients were similar, and mostly displayed quantitative rather than qualitative differences from normal pattern. Biotin-labeled lectins were used to evaluate quantitative differences in the glycoforms of Hpt from plasma and psoriatic skin scales. Hpt from skin and plasma of patients showed more fucosylated and branched glycans than Hpt from plasma of healthy subjects. Tryptic glycopeptides of Hpt were also analyzed by mass spectrometry, and a decreased amount of sialylated glycan chains was found in glycopeptides of skin Hpt, as compared with Hpt from plasma. High levels of glycans with fucosylated and tetra-antennary chains were detected on the peptide NLFLNHSENATAK from Hpt of psoriatic patients. Our data demonstrate that specific changes in glycan structures of Hpt, such as enhanced glycan branching and fucose content, are associated with psoriasis, and that differences between circulating and skin Hpt do exist. A lower extent of glycan fucosylation and branching was found in Hpt from plasma of patients in disease remission. Altered glycoforms might reflect changes of Hpt function in the skin, and could be used as markers of the disease.
PLoS ONE 01/2012; 7(12):e52040. · 4.09 Impact Factor
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ABSTRACT: Leptin belongs to the helical cytokine family and has structural similarity to interleukin (IL)-6, IL-12, IL-15, prolactin, and growth hormone. It is mainly secreted by adipocytes but (at lower levels) also by stomach, skeletal muscle, and placenta. Initially, leptin was considered an antiobesity hormone, but experimental evidence has also shown pleiotropic effects on hematopoiesis, angiogenesis, lymphoid organ homeostasis, and T-lymphocyte functions. Recent evidence indicates that leptin modifies T-cell immunity by promoting T helper 1 proinflammatory immune response and production of cytokines.
The aim of the present study was to evaluate leptin serum levels in patients with allergic contact dermatitis (ACD) and atopic dermatitis and to evaluate the correlation of these levels with different patterns of lymphocyte subpopulations.
Serum leptin was assayed by enzyme-linked immunosorbent assay. Immunophenotypic analysis of peripheral blood was performed by flow cytometry.
We found that serum leptin levels were higher in ACD patients than in healthy controls (p = .02). In these patients, an inverse correlation between serum leptin and the percentage of CD4CD25 T lymphocytes was observed (p = .002).
These data seem to suggest that leptin might play a role in the pathogenesis of ACD and thus have implications for the therapy for ACD.
Dermatitis 11/2011; 22(6):320-3. · 1.21 Impact Factor
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Journal of the American Academy of Dermatology 06/2011; 64(6):1200-2. · 3.99 Impact Factor
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Gabriella Fabbrocini,
Stefania Staibano,
Giuseppe De Rosa,
Valeria Battimiello,
Nunzio Fardella,
Gennaro Ilardi,
Maria Immacolata La Rotonda,
Amelia Longobardi,
Marialuisa Mazzella,
Maria Siano,
Francesco Pastore,
Valerio De Vita,
Maria Luisa Vecchione, Fabio Ayala
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ABSTRACT: Acne vulgaris is a complex, chronic, and common skin disorder of pilosebaceous units. The major pathogenic factors involved are ductal hyperkeratinization, obstruction of sebaceous follicles resulting from abnormal keratinization of the infundibular epithelium, stimulation of sebaceous gland secretion by androgens, and microbial colonization of pilosebaceous units by Propionibacterium acnes, which promotes perifollicular inflammation.
The aim of the study was to investigate the therapeutic effects of resveratrol, a natural phytoalexin produced by some spermatophytes, such as grapes and other plants, on acneic skin.
Resveratrol was incorporated in a carboxymethylcellulose-based gel. The chemical stability of resveratrol after storage at 4°C for 30 days was investigated by high-performance liquid chromatography (HPLC). The resveratrol-containing hydrogel was administered to 20 patients affected by acne vulgaris enrolled in this single-blind study. The resveratrol-containing formulation was applied daily as a solo treatment on the right side of the face for 60 days, while the hydrogel vehicle was applied to the left side of the face as a control. To objectively evaluate the results, a digital photographic database was used to collect images. The number and type of lesions were recorded for each patient, to compare the Global Acne Grading System (GAGS) score before treatment with that obtained at the end of the study. Moreover, with the innovative technique of follicular biopsy, areas of acneic skin were prepared for histopathology. The average area occupied by microcomedones at baseline was compared with that at the end of treatment.
HPLC analysis demonstrated that resveratrol, upon incorporation into the gel, did not convert to its cis-isomer when stored at 4°C for 30 days. All patients were satisfied with the active treatment and none experienced adverse effects. Clinical evaluation showed a 53.75% mean reduction in the GAGS score on the resveratrol-treated sides of the face compared with 6.10% on the vehicle-treated sides of the face. These data were supported by histologic analysis, which showed a 66.7% mean reduction in the average area of microcomedones on the resveratrol-treated sides of the face. The comparison with the vehicle-treated side of the face (9.7% reduction) showed a clinically relevant and statistically significant decrease of lesions in areas treated with resveratrol-containing hydrogel.
This pilot study showed positive results for resveratrol gel in acne, and should be considered a valid starting point for further testing of the effectiveness of this molecule in different concentrations and formulations and in a larger group of patients.
American Journal of Clinical Dermatology 04/2011; 12(2):133-41. · 1.71 Impact Factor
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ABSTRACT: 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.
Experimental Dermatology 03/2011; 20(3):288-90. · 3.54 Impact Factor
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Bernardetta Maresca,
Luisa Cigliano,
Maria M Corsaro,
Giuseppina Pieretti,
Massimo Natale,
Enrico M Bucci,
Fabrizio Dal Piaz,
Nicola Balato,
Massimiliano Nino, Fabio Ayala,
Paolo Abrescia
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ABSTRACT: 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.
Biological Chemistry 12/2010; 391(12):1429-39. · 2.96 Impact Factor
