Alberto Giannetti

Prevalence of metabolic syndrome in patients with psoriasis: a hospital‐based case–control study

Background  Psoriasis is a chronic inflammatory disease associated with an increased cardiovascular risk. Metabolic syndrome is a significant predictor of cardiovascular events.

Correction of junctional epidermolysis bullosa by transplantation of genetically modified epidermal stem cells

The continuous renewal of human epidermis is sustained by stem cells contained in the epidermal basal layer and in hair follicles. Cultured keratinocyte stem cells, known as holoclones, generate sheets of epithelium used to restore severe skin, mucosal and corneal defects. Mutations in genes encoding the basement membrane component laminin 5 (LAM5) cause junctional epidermolysis bullosa (JEB), a devastating and often fatal skin adhesion disorder. Epidermal stem cells from an adult patient affected by LAM5-β3–deficient JEB were transduced with a retroviral vector expressing LAMB3 cDNA (encoding LAM5-β3), and used to prepare genetically corrected cultured epidermal grafts. Nine grafts were transplanted onto surgically prepared regions of the patients legs. Engraftment was complete after 8 d. Synthesis and proper assembly of normal levels of functional LAM5 were observed, together with the development of a firmly adherent epidermis that remained stable for the duration of the follow-up (1 year) in the absence of blisters, infections, inflammation or immune response. Retroviral integration site analysis indicated that the regenerated epidermis is maintained by a defined repertoire of transduced stem cells. These data show that ex vivo gene therapy of JEB is feasible and leads to full functional correction of the disease.

Ceramide and Cholesterol Composition of the Skin of Patients with Atopic Dermatitis

Atopic dermatitis skin tends to be easily irritated and appears dry. These clinical peculiarities correspond to impaired barrier function and to increased transepidermal water loss (TEWL) values. A few studies suggest that a reduced amount of total ceramides (especially of ceramide 1) is responsible for functional abnormalities of the skin of atopic dermatitis patients. The aim of this study was to analyze the relationship between epidermal lipids and barrier impairment in the skin of patients with atopic dermatitis. The quantity of ceramides, cholesterol sulphate and free cholesterol of 47 patients with atopic dermatitis and 20 age- and sex-matched healthy subjects was assessed by cyanoacrylate stripping and thin layer chromatography. Capacitance and TEWL were recorded at the same site of the lipid sample. In patients with atopic dermatitis, the levels of ceramide 1 and 3 were significantly lower and values of cholesterol significantly higher with respect to healthy subjects. Moreover, the CER/CH ratio was significantly lower with respect to normal skin. Patients with active signs of eczema also had higher TEWL values and lower capacitance values. By contrast, patients with no active signs of atopic dermatitis had a normal barrier function and intermediate values of ceramides and cholesterols, when compared to patients with atopic dermatitis with active lesions and normal subjects. The quantity of ceramide 3 was significantly correlated with TEWL impairment. These findings suggest that a decrease in ceramides in the stratum corneum is involved in barrier impairment in atopic dermatitis skin. Our data confirm those of other authors and support the view that impaired metabolism of ceramides may be the cause of dry skin and impaired barrier function in atopic dermatitis.

Primary cutaneous marginal zone B-cell lymphoma : A recently described entity of low-grade malignant cutaneous B-cell lymphoma

Recently a new classification of primary cutaneous B-cell lymphomas (PCBCLs) has been proposed by the European Organization for Research and Treatment of Cancer (EORTC)--Cutaneous Lymphoma Project Group. The marginal zone B-cell lymphomas (MZLs) were not included as a distinct entity because of insufficient experience and controversial opinions. We have studied 32 patients (M:F ratio 1.5:1; age range 25-93 years; mean age 49.6 years; median age 50 years) to determine the diagnostic criteria of primary cutaneous MZL and the relationship with other low-grade malignant PCBCLs. For comparison, three patients with immunocytoma were included in the study. Clinically, patients presented with solitary or clustered reddish or red-brown papules, nodules, and plaques, sometimes surrounded by an erythematous halo. Histopathologic sections showed nodular or diffuse infiltrates involving the dermis and subcutaneous fat. Cytomorphologically small to medium-sized cells with indented nuclei and abundant pale cytoplasm (marginal zone cells, centrocyte-like cells) predominated. In addition, scattered blasts, lymphoplasmacytoid cells, and plasma cells were observed below the epidermis and at the periphery of the infiltrates. Reactive germinal centers were present in 75% of the cases. The three cases of immunocytoma showed a more monomorphous pattern with predominance of lymphoplasmacytoid cells. The marginal zone cells showed a CD20+, CD79a+, CD5- and Bcl-2+ immunophenotype. They expressed immunoglobulin G in the majority of the cases. Staining with the monocytoid B cell-related antibody KiM1p gave positive results in all specimens with a typical intracytoplasmic granular pattern. A monoclonal distribution of immunoglobulin light chains was observed in marginal zone cells in 75% of the cases. Germinal centers, when present, were either polyclonal or negative for both kappa and lambda light chains. Monoclonal rearrangement of the JH gene was detected via polymerase chain reaction (PCR) in 18 of 26 investigated specimens. Analysis in 12 patients of the bcl-2/immunoglobulin heavy chain gene rearrangement using PCR yielded negative results. Lesions were treated by surgical excision followed in some patients by local radiotherapy. Systemic antibiotic therapy was administered to three patients, with good response in two. The prognosis is excellent. After a mean follow-up of 47.9 months (range 6-252; median 24) all patients are alive without signs of systemic lymphoma. Primary cutaneous MZL represents a distinct clinicopathologic subtype of low-grade malignant PCBCL.

International Consensus Conference on Atopic Dermatitis II (ICCAD II): clinical update and current treatment strategies

C . E L L I S * A N D T . L U G E R † O N B E H A L F O F T H E I C C A D I I F A C U L T Y : D . A B E C K , R . A L L E N , R . A . C . G R A H A M B R O W N , Y . D E P R O S T , L . F . E I C H E N F I E L D , C . F E R R A N D I Z , A . G I A N N E T T I , J . H A N I F I N , J . Y . M . K O O , D . L E U N G , C . L Y N D E , J . R I N G , R . R U I Z M A L D O N A D O A N D J H . S A U R A T

Granulocyte macrophage colony-stimulating factor is overproduced by keratinocytes in atopic dermatitis. Implications for sustained dendritic cell activation in the skin.

Lesional skin of atopic dermatitis (AD) harbors high numbers of dendritic cells with enhanced stimulatory capacity for T lymphocytes. In this study, lesional AD skin was shown to stain heavily in both epidermal and dermal compartments for GM-CSF, a cytokine crucial to dendritic cell functions. Keratinocyte cultures established from uninvolved skin of AD patients exhibited markedly increased spontaneous and PMA-stimulated release of GM-CSF compared with keratinocytes from nonatopic controls. Correspondingly, keratinocytes from AD patients showed higher constitutive as well as PMA-induced GM-CSF gene expression. Larger amounts of GM-CSF were produced by AD keratinocytes, also in response to IL-1alpha, but not after stimulation with LPS, lipoteichoic acid, or staphylococcal enterotoxin B. Hydrocortisone reduced GM-CSF gene expression and protein release in both atopic and control keratinocytes. Supernatants from atopic keratinocytes were able to strongly stimulate PBMC proliferation in a GM-CSF-dependent manner. Moreover, conditioned medium from PMA-treated AD keratinocytes, together with exogenous IL-4, could support phenotypical and functional maturation of peripheral blood precursors into dendritic cells. Enhanced production of GM-CSF by keratinocytes may contribute relevantly to the establishment and chronicity of AD lesions, in particular to the increased number, sustained activation, and enhanced antigen-presenting functions of dendritic cells.

Proactive treatment of atopic dermatitis in adults with 0.1% tacrolimus ointment

Background:  Long‐term treatment for atopic dermatitis (AD) using low dose, intermittent, topical anti‐inflammatory agents may control acute disease and prevent relapses. This 12‐month, European, multicentre, randomized study investigated whether the proactive use of 0.1% tacrolimus ointment applied twice weekly can keep AD in remission and reduce the incidence of disease exacerbations (DE).

Impact of Body Mass Index and Obesity on Clinical Response to Systemic Treatment for Psoriasis

Objective: Our aim was to assess the role of the body mass index (BMI) in the clinical response to systemic treatment for psoriasis. Methods: A nationwide cohort study of patients receiving a new systemic treatment for plaque psoriasis at reference centres in Italy was conducted. Information was gathered through a web-based electronic form. Patients being maintained on the same medication and with data available at 8 and 16 weeks by March 31, 2007, were eligible. The outcome was a reduction in the Psoriasis Area Severity Index (PASI) of at least 75% at follow-up compared to baseline (PASI-75). Results: Out of 8,072 patients enrolled, 2,368 were eligible and analysable at 8 weeks and 2,042 at 16 weeks. PASI-75 was achieved by 819 patients (34.5%) at 8 weeks and 1,034 (50.6%) at 16 weeks. The proportion steadily decreased with increased values of BMI. Compared to normal weight (BMI = 20–24) the adjusted odds ratio for achieving PASI-75 in obese patients was 0.73 (95% CI = 0.58–0.93) at 8 weeks and 0.62 (95% CI = 0.49–0.79) at 16 weeks. The impact of the BMI did not show remarkable variations according to the drug prescribed at entry. Conclusion: The BMI affects the early clinical response to systemic treatment for psoriasis.

Neuropeptides in skin from patients with atopic dermatitis: an immunohistochemical study

The distribution and localization of several neuropeptides were investigated in the lichenified lesions of 11 patients with atopic dermatitis using indirect immunofluorescence. Substance P‐positive nerve fibres were observed in most of the cases of atopic dermatitis, but not in normal controls. Somatostatin immunoreactive nerves were not found in the skin of atopic dermatitis, whereas a normal pattern of immunoreactivity could be detected in most of the healthy subjects. Neuropeptide Y‐positive dendritic epidermal cells were observed in lesional skin from patients with atopic dermatitis, but not in controls. Calcitonin gene‐related peptide and vasoactive intestinal polypeptide immunoreactivity in patients with atopic dermatitis did not differ from that in healthy subjects. With galanin antiserum a diffuse intracellular staining was observed in the epidermis of both atopic patients and controls, while no positive staining was found with either neurotensin or neurokinin A antibodies in either group. These findings suggest a possible involvement of some neuropeptides in the pathomechanisms of atopic dermatitis.

Echographic Evaluation with Image Analysis of Normal Skin: Variations according to Age and Sex

In order to identify and characterize the sonographic variations between different age groups, 48 subjects, 24 aged 27-30, and 24 over 60, were studied with a 20-MHz B scanner on six skin sites. Images were evaluated by the instruments standard programme and by a new image analysis software package enabling the characterization of steady structures or transitory functional aspects of skin reactions, by highlighting areas in which the echo amplitudes are included within selected values, and by calculating their extension. Three bands were selected as intervals of interest, respectively, highlighting hyporeflecting parts of the dermis, tissue reflecting with intermediate amplitude values and hyperreflecting epidermis and dermis. This method was employed to assess skin thickness, demonstrating its decrease in elderly skin, to characterize and quantify the hypoechogenic subepidermal band appearing in the elderly at volar and dorsal forearm skin, and to evaluate echogenicity of the upper and lower dermis. Our data show that there is a great regional variation in the behaviour of ultrasound reflection of elderly skin in respect to the skin of young subjects. However, a general trend can be identified, consisting in a shift from low-intensity ultrasound echoes, characteristic in the dermis of young subjects, to intermediate or high reflection amplitudes, which are more frequent in elderly skin. Thus, the echographic method provides two parameters for the evaluation of skin aging.(ABSTRACT TRUNCATED AT 250 WORDS)