Optical coherence tomography for patch test grading: A prospective study on its use for noninvasive diagnosis of allergic contact dermatitis.

BACKGROUND: The diagnosis of allergic contact dermatitis should be confirmed by skin patch tests. Distinguishing between irritant and allergic reactions is sometimes difficult. OBJECTIVES: To analyse the in vivo morphological changes in patch test reactions compared to healthy skin, and to detect subclinical changes in doubtful reactions using optical coherence tomography (OCT). To develop an OCT-based algorithm to support patch-test grading. METHODS: One hundred twenty-nine skin patch-test areas were scanned with OCT to evaluate the following features: architectural and vascular morphology, epidermal thickness, optical attenuation coefficient (AC), and blood flow at 0.1, 0.2, and 0.35 mm depth. RESULTS: Most common OCT features of acute contact allergic reactions in patch tests were spongiosis with microvesicles (94.8%), macrovesicles (60.3%), and coalescing vesicles (46.6%), the latter useful in differentiating acute allergic from irritant dermatitis (P-value < .05). Objective quantitative parameters correlated well with the severity grade: epidermal thickness due to spongiosis, AC (P-value < .05) and blood flow at 0.2 and 0.35 mm (P-value < .01). CONCLUSIONS: OCT as a noninvasive diagnostic tool, established for skin cancer diagnosis, is useful for evaluating contact allergic patch-test reactions. Not only morphological but also objective features such as blood flow and AC correlate with the reaction severity. Further studies are needed to explore the differences in irritant and allergic contact dermatitis.

In Vivo Reflectance Confocal Microscopy: Emerging Role in Noninvasive Diagnosis and Monitoring of Eczematous Dermatoses. / Microscopia confocal de reflectancia in vivo: papel emergente en el diagnóstico no invasivo, así como en el seguimiento de las dermatosis eccematosas.

Dermatologic diagnosis and monitoring have been dependent largely on visual grading. A skin biopsy is performed in case of diagnostic uncertainty, but can be traumatic, and results are delayed due to time for specimen transport and processing. Biopsies also destroy specimens, prohibiting lesion evolution monitoring. In vivo reflectance confocal microscopy (RCM) offers a diagnostic alternative to skin biopsy. RCM captures real-time, high-resolution images, and has been piloted for the evaluation of various dermatologic conditions. Identification of unique RCM features may distinguish dermatoses with similar clinical morphologies. Allergic contact dermatitis (ACD) and irritant contact dermatitis (ICD) are diagnosed by patch testing that currently uses a subjective scoring system. RCM has increasingly been studied for early detection and severity grading of CD. Common RCM features shared by ACD and ICD are stratum corneum disruption, vesicle formation, exocytosis, spongiosis, and parakeratosis. Features unique to ACD are vasodilation, increased epidermal thickness, intercellular edema, and acanthosis. Features unique to ICD are detached corneocytes and targetoid keratinocytes. This review summarizes the use of RCM in evaluating contact eccematous conditions and aims to spark future research and interest in this promising tool.

A Non-Peptidic S100A9 Specific Ligand for Optical Imaging of Phagocyte Activity In Vivo.

PURPOSE: Non-invasive assessment of inflammatory activity in the course of various diseases is a largely unmet clinical challenge. An early feature of inflammation is local secretion of the alarmin S100A8/A9 by activated phagocytes. We here evaluate a novel S100A9-targeted small molecule tracer Cy5.5-CES271 for in vivo optical imaging of inflammatory activity in exemplary disease models. PROCEDURES: Dynamics of Cy5.5-CES271 was characterized in a model of irritant contact dermatitis by sequential fluorescence reflectance imaging (FRI) up to 24 h postinjection (p.i.). Specificity of Cy5.5-CES271 binding to S100A9 in vivo was examined by blocking studies and by employing S100A9-/- mice. Finally, S100A9 secretion in acute lung inflammation was assessed by Cy5.5-CES271 and FRI of explanted lungs. RESULTS: In ear inflammation, we were able to non-invasively follow the time course of S100A9 expression using Cy5.5-CES271 and FRI over 24 h p.i. (peak activity at 3 h p.i.). Specificity of imaging could be shown by a significant signal reduction after predosing and using S100A9-/- mice. In acute lung injury, local and systemic S100A8/A9 levels increased over time and correlated significantly with FRI signal levels in explanted lungs. CONCLUSIONS: Cy5.5-CES271 shows significant accumulation in models of inflammatory diseases and specific binding to S100A9 in vivo. This study, for the first time, demonstrates the potential of a small molecule non-peptidic tracer enabling imaging of S100A9 as a marker of local phagocyte activity in inflammatory scenarios suggesting this compound class for translational attempts.

Ultrasound description and quantification of irritant reactions induced by dithranol at different concentrations. A comparison with visual assessment and colorimetric measurements.

Dithranol (D) is used as a therapeutic topical agent to treat psoriasis, although it produces inflammation and staining of skin and clothing. D-induced irritation has been evaluated by visual scoring and by bioengineering techniques, evidencing modifications of the inflammatory parameters, but no alterations of the skin barrier. The aim of our study was to evaluate the irritant reactions induced by D using ultrasound, and to compare the B-scanning data with visual assessments and colorimetric measurements. 13 healthy women underwent 2, 3-h patch tests with, respectively, 0.02% and 0.1% D in white petrolatum and 1 24-h patch test with 2% sodium lauryl sulfate (SLS). For assessing skin reactions, clinical judgement, colorimetry and echography were employed. Echographic images were evaluated by skin thickness measurements and segmentation procedures, using an 0-30 interval, marking the hyporeflecting areas in the dermis, and a 201-255 interval, assessing the hyperreflecting components of the image (both epidermal and dermal). In all subjects, D produced uniform reactions, the intensity varying according to concentration. Both echographic parameters of inflammation (skin thickness and 0-30 areas) showed an increase at all times of assessment. The 201-255D/0-30 pixel ratio, describing the distribution of dermal edema, indicated that strong inflammatory reactions, such as those caused by the application of 0.1% D, are accompanied by edema in the lower portion of the dermis. Finally, in contrast to SLS reactions, where a 24-h reduction in epidermal reflectivity was observable, D reactions appeared with an accentuation of the 201-255 epidermal band at 24-96-h examinations.

Sodium hydroxide-induced irritant dermatitis as assessed by computerized elaboration of 20 MHz B-scan images and by TEWL measurement: a method for investigating skin barrier function.

Sodium hydroxide-induced irritation was studied in 34 volunteers, by means of 24-h patch testing at different concentrations, and by a 10-min testing procedure employing 0.1 mol/l NaOH. As a supplement to subjective evaluation of skin changes, assessments of test areas by TEWL measurement and sonography were performed at 24, 48 and 72 h. After 24-h patch testing, instrumental evaluations showed an increase in the extension of the hypo-echogenic dermal area and in TEWL, whereas a 10-min NaOH application induced a decrease of the dermal and epidermal reflectivity and an increase in TEWL. Twenty-four hour patch testing with 4% NaOH allowed a classification of subjects into two categories: subjects who reacted normally and hyper-reactors. Hyper-reactors showed an enhanced inflammatory response and a more pronounced barrier function damage, as assessed clinically and instrumentally by decreased dermal reflectivity, and by higher postexposure TEWL. Subjects with a more marked inflammatory response to 4% NaOH also showed greater TEWL increases during the short-term testing procedure employing 0.1 mol/l NaOH. Moreover, these subjects were characterized by higher baseline TEWL values, indicating that cutaneous reactivity to NaOH is at least partly correlated to impaired stratum corneum function, which is inadequate to effectively prevent compounds from penetrating the skin.

Echographic evaluation with image analysis of irritant reactions induced by nonanoic acid and hydrochloric acid.

Skin reactions to 40% nonanoic acid in propanol (NON) and to 4% hydrochloric acid were evaluated by image analysis of 20 MHz B scan recordings (Dermascan C, Cortex Technology). 18 women, aged 18 to 45, were patch tested with 24-h application time, and clinical and instrumental evaluations were performed at the beginning of the experiment, and 24 and 48 h after patch testing. To check possible regional variations in reactivity to NON and HCl, both substances were applied 2 x on the same forearm. As control tests, saline solution, propanol and sodium lauryl sulfate (SLS) 3% were applied. Echographic images were processed by a program enabling numerical representation of picture data, based on attribution of fictional values to the echoes' amplitudes, selection of amplitude bands of interest, binary transformation of the image, and calculation of the extension of areas reflecting within the same amplitude range. Sonographic recordings were evaluated by an amplitude interval marking hyporeflecting parts of the dermis (corresponding to edema and inflammatory infiltration), and by a band highlighting the entrance echo (epidermis). Our evaluations showed that extension of the hypoechogenic area of the dermis increases according to intensity of inflammatory reaction for all irritant substances. A clear decrease in reflectivity of the epidermis echo at 24 h was visible at SLS patch test test sites, whereas at patch test sites performed with NON and HCl, there was a trend towards an increase in values of hyperreflecting pixels. No significant variations between data recorded at proximal compared to distal skin sites were observed for NON and HCl. In conclusion, the echographic technique provides a method for quantification of the dermal inflammatory reaction, and also for description of skin reactions induced by irritant substances, according to their specific epidermal effects.