Stefania Seidenari

Guidelines for treatment of atopic eczema (atopic dermatitis) Part I.

The existing evidence for treatment of atopic eczema (atopic dermatitis, AE) is evaluated using the national standard Appraisal of Guidelines Research and Evaluation. The consensus process consisted of a nominal group process and a DELPHI procedure. Management of AE must consider the individual symptomatic variability of the disease. Basic therapy is focused on hydrating topical treatment, and avoidance of specific and unspecific provocation factors. Anti‐inflammatory treatment based on topical glucocorticosteroids and topical calcineurin inhibitors (TCI) is used for exacerbation management and more recently for proactive therapy in selected cases. Topical corticosteroids remain the mainstay of therapy, but the TCI tacrolimus and pimecrolimus are preferred in certain locations. Systemic immune‐suppressive treatment is an option for severe refractory cases. Microbial colonization and superinfection may induce disease exacerbation and can justify additional antimicrobial treatment. Adjuvant therapy includes UV irradiation preferably with UVA1 wavelength or UVB 311 nm. Dietary recommendations should be specific and given only in diagnosed individual food allergy. Allergen‐specific immunotherapy to aeroallergens may be useful in selected cases. Stress‐induced exacerbations may make psychosomatic counselling recommendable. ‘Eczema school’ educational programs have been proven to be helpful. Pruritus is targeted with the majority of the recommended therapies, but some patients need additional antipruritic therapies.

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.

The prevalence of positive reactions in the atopy patch test with aeroallergens and food allergens in subjects with atopic eczema: a European multicenter study

Background:  The atopy patch test (APT) was proposed to evaluate IgE‐mediated sensitizations in patients with atopic eczema (AE).

ETFAD/EADV eczema task force 2009 position paper on diagnosis and treatment of atopic dermatitis

Background  The diagnosis of atopic dermatitis (AD) is made using evaluated clinical criteria. Management of AD must consider the symptomatic variability of the disease.

Monitoring levels of preservative sensitivity in Europe - A 10-year overview (1991-2000)

A 10‐year multicentre analysis of the frequency of sensitivity to common preservatives collected in 16 centres in 11 countries has shown stable but persisting high levels of sensitivity to formaldehyde and 5‐chloro‐2‐methyl‐4‐isothiazolin‐3‐one + 2‐methyl‐4‐isothiazolin‐3‐one (MCI/MI). It has also revealed a significant increase in the level of reactivity to methyldibromoglutaronitrile (MDBGN) from 0.7% in 1991 to 3.5% in 2000. The current high level of sensitivity to MDBGN requires an urgent safety re‐evaluation and risk assessment update along with consideration of immediate lowering of use concentrations, especially in leave‐on products.

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.

Baseline biophysical parameters in subjects with sensitive skin

Sensitive skin has been described as a skin type showing higher reactivity than normal skin and developing exaggerated reactions when exposed to external factors. The stinging test, performed by applying lactic acid to the nasolabial fold and evaluating the intensity of subjective symptoms, is widely accepted as a marker of sensitivity and employed for the selection of subjects experiencing invisible cutaneous irritation. However, this test is based on self‐perceived assessment and lacks objectivity. In order to contribute to the finding of objective descriptors, we assessed baseline biophysical parameters in subjects with sensitive skin by means of transepidermal water loss (TEWL), capacitance, pH, sebum and skin colour measurements, and compared the data with those obtained in normal subjects, also correlating the results with those of clinical assessments and functional tests. Subjects with sensitive skin showed a trend towards higher scores at all assessment times both for the stinging and the washing test. The skin of sensitive subjects was described as less supple, less hydrated and more erythematous and telangiectatic with respect to the skin of normal subjects. A trend towards an increase in TEWL, pH and colorimetric a* values, and a decrease in capacitance, sebum and colorimetric L* values on the face of subjects with sensitive skin was observable. However, significances were only present for capacitance and a* values. Thus, alterations of baseline capacitance values indicate the tendency to barrier impairment and support the view that skin hyperreactivity to water‐soluble irritants is induced by a greater amount of irritants absorbed, whereas the increase in the erythema parameter shows that cutaneous vascular hyperreactivity in subjects with sensitive skin also corresponds to baseline vasodilation.

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)

In Vivo Confocal Microscopic and Histopathologic Correlations of Dermoscopic Features in 202 Melanocytic Lesions

OBJECTIVES To identify in vivo microscopic substrates of the dermoscopic patterns of melanocytic lesions and to correlate them with histopathologic features. DESIGN Before excision, lesion areas that showed characteristic dermoscopic patterns were imaged by dermoscopy and confocal microscopy and directly correlated with histopathologic features. SETTING Departments of Dermatology of the University of Modena and Reggio Emilia and Hospital Clínico of Barcelona, between July 2006 and March 2007. Patients Patients with 202 melanocytic lesions, corresponding to 76 melanomas, 114 nevi, and 12 Spitz or Reed nevi. MAIN OUTCOME MEASURES Correlation of dermoscopic patterns in melanocytic lesions with confocal microscopic findings and conventional histopathologic findings. RESULTS Characteristic architectural and cytologic substrates were identified in vivo with the use of confocal microscopy and correlated with histopathologic features. Pigment network atypia was evidenced through confocal microscopy as a disarrangement of dermoepidermal junction architecture and cellular atypia. Pigmented globules consisted of cell clusters, corresponding to melanocytic nests identified on histopathologic analysis. Black dots correlated with intraepidermal reflective spots or with large pagetoid cells in nevi and melanoma, respectively. Blue structures usually consisted of numerous pleomorphic cells, corresponding to malignant melanocytes and inflammatory cells in melanomas, whereas plump bright cells, corresponding to melanophages on histopathologic analysis, characterized benign lesions. Within regression, a retiform distribution of collagen fibers, which sometimes intermingled with melanophages and rarely with nucleated cells, was observable. CONCLUSIONS The knowledge of the cytologic and architectural aspects of the different dermoscopic patterns, as they appear by in vivo confocal microscopy, may guide the user to the identification of specific substrates in melanocytic lesions and consequently the interpretation of the dermoscopic features.

In Vivo Reflectance Confocal Microscopy Enhances Secondary Evaluation of Melanocytic Lesions

We recently described an in vivo reflectance confocal microscopy (RCM) method and our aim was to evaluate a possible additive value of this type of analysis in the management of melanocytic lesions. In two referral centers (Sydney and Modena), lesions (203 nevi and 123 melanomas (MMs) with a median Breslow thickness of 0.54 mm) were excised on the basis of clinical suspicion (history, dermoscopy examination, and/or digital monitoring). The RCM method was also trialed on a non-biopsied population of 100 lesions, which were clinically and dermoscopically diagnosed as benign nevi. All RCM and dermoscopy diagnoses were performed blinded to the histopathological diagnosis. Firstly, in the study population, a high interobserver agreement (on a subset of 90 lesions) was seen with the RCM method, which had superior specificity (68%, 95% confidence interval (95% CI): 61.1-74.3) for the diagnosis of MM compared with dermoscopy (32%, 95% CI: 25.9-38.7), while showing no difference in sensitivity (91%, 95% CI: 84.6-95.5, RCM; 88%, 95% CI: 80.7-92.6 dermoscopy). The two techniques had a weak correlation, resulting in only 2.4% of MMs being misclassified by both techniques. Diagnosis of light-colored lesions is improved by RCM (specificity 84%, 95% CI: 66.3-94.5) compared with dermoscopy (specificity 39%, 95% CI: 23.7-56.2). Secondly, the RCM method classified 100% of the non-biopsied control nevi population as benign.