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and bright &#40;reflecting&#41; structures within seconds&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">4</span></a> This corresponds to a boundary between two separate cellular structures that have different indices of refraction&#44; including&#44; but not limited to membranes&#44; inflammatory debris&#44; and melanosomes&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">4</span></a> Light is reflected back towards an objective lens&#46; Prior&#44; a pinhole aperture filters out scattered light to create a high-resolution image similar to conventional histology&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">4&#44;5</span></a> Each image collected is viewed in a 500<span class="elsevierStyleHsp" style=""></span>&#956;m<span class="elsevierStyleSup">2</span> &#8211; 8<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleSup">2</span> field of view with 30X magnification&#46; The device captures multiple images in two-dimensions with horizontal image stacking &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>B&#41;&#44; which differs from vertical sectioning of standard histopathology&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">5</span></a> Single laser RCM devices are handheld&#44; conferring ease of use&#46; Multi-laser devices combine fluorescent light spectrum microscopy and RCM&#46; Fluorescent light spectrum microscopy augments the wavelength spectrum to identify more features of normal and pathologic skin&#46; RCM has some advantages over dermoscopy as it can magnify cellular structures and features unique to each skin layer&#44; and collect time-lapse photography to allow detection of dynamic skin changes&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">6</span></a> Additionally&#44; detection of subclinical changes by RCM allows for early treatment implementation and prevents premature treatment termination&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">7</span></a> RCM imaging may also reduce participation commitment for both patients and clinicians&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">8</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Contact Dermatoses</span><p id="par0015" class="elsevierStylePara elsevierViewall">Approximately 20&#37; of the U&#46;S&#46; population is affected by contact dermatitis &#40;CD&#41;&#44; which account for up to 95&#37; of occupational dermatoses&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">9</span></a> Allergic contact dermatitis &#40;ACD&#41; occurs when contact with a particular substance elicits a delayed Type-IV hypersensitivity reaction that necessitates a 10-14 day sensitization phase&#46; Upon allergen re-exposure&#44; the reaction develops within 24-48<span class="elsevierStyleHsp" style=""></span>hours&#46; ACD manifests as pruritic&#44; erythematous&#44; scaly&#44; edematous plaques with vesiculation at the sites of exposure&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">10</span></a> Histologically&#44; ACD presents with vesicle formation&#44; inflammatory infiltrate&#44; and spongiosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">11&#8211;13</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Whereas ACD requires prior exposure to elicit a cutaneous response&#44; irritant contact dermatitis &#40;ICD&#41; can result from a singular exposure to an irritant&#46; ICD presents with erythema&#44; fissuring&#44; and xerosis&#44; typically with more burning and less itching than ACD&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">10</span></a> Histologically&#44; ICD causes significant stratum corneum &#40;SC&#41; disruption&#44; parakeratosis&#44; and increased epidermal thickness&#46; Despite differences in patho-etiology&#44; ACD and ICD may have similar morphology&#44; and are often difficult to distinguish based on visual inspection alone&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">14</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Patch testing &#40;PT&#41; is the current gold standard to elicit CD&#44; followed by clinician interpretation using the International Contact Dermatitis Research Group scoring system &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; The scoring system has a sensitivity and specificity of 85&#37;&#44; with a 15-18&#37; false-positive rate&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">15</span></a> Evaluation of cutaneous reactions is highly subjected to inter- and intra-grader variability&#46; It is important to note that the same criteria are used for diagnosing both ACD and ICD&#44; with no standardized parameter to differentiate the two&#46; Thus&#44; there is a practical need to provide more consistent and objective grading in CD&#46; <a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">RCM has been used to distinguish eczematous conditions with similar morphologies&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">4</span></a> Early reaction detection by RCM may reduce the need for subsequent visits to grade delayed hypersensitivity reactions&#44; and allow for early treatment implementation&#46; In 2015&#44; Hoogedoorn et al&#46; briefly discussed ACD and ICD in their systematic review of the RCM literature on inflammatory skin diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">16</span></a> Our updated in-depth review summarizes current evidence on the emerging use of RCM for diagnosis and monitoring of contact eczematous conditions&#44; including ACD and ICD&#46;</p></span></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">MATERIALS AND METHODS</span><p id="par0035" class="elsevierStylePara elsevierViewall">In October 2017&#44; two research personnel conducted a literature review to explore established RCM features of CD&#46; PubMed and Google Scholar websites were searched using the terms &#8216;reflectance confocal microscopy&#8217; AND &#8216;eczematous dermatoses&#44;&#8217; OR &#8216;dermatitis&#44;&#8217; OR &#8216;allergic contact dermatitis&#44;&#8217; OR &#8216;irritant contact dermatitis&#46;&#8217; These search parameters yielded a total of 49 papers&#46; Literature selection was limited by publications or translations in the English language and randomized controlled trials &#40;RCT&#41;&#46; Three publications were excluded due to their primary discussion of laser scanning microscopy or fluorescence confocal microscopy&#46; The 10 studies included in this review involved the use of RCM in RCT&#44; and are summarized in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">REVIEW OF LITERATURE</span><p id="par0040" class="elsevierStylePara elsevierViewall">Koller <span class="elsevierStyleItalic">et al</span>&#46; evaluated the validity of RCM in diagnosing CD&#46; Twenty CD lesions and 10 healthy tissue controls were confirmed by histology &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9&#41; or positive PT &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41;&#44; and verified by three independent dermatologists who had moderate RCM grading experience&#46; RCM detected CD with 83&#37; sensitivity and 92&#37; specificity and healthy skin with 97&#37; sensitivity and 99&#37; specificity&#46; The authors attributed these statistical differences to more complex morphologic features in CD&#46; Features present in CD RCM images were exocytosis&#44; epidermal edema&#44; and dermal vasodilatation&#46; Intraepidermal vesicle formation in the upper epidermis and dermo-epidermal junction had high inter-observer agreement&#46; When using these two features alone&#44; classification tree software analysis accurately identified 82&#37; of CD lesions&#46; However&#44; with only 20 CD lesions analyzed&#44; it&#39;s unclear if these findings can be generalized to the overall population&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">17</span></a> The authors made no distinction between ACD and ICD&#46; Nevertheless&#44; the findings offer potential for further exploration comparing ACD and ICD reactions&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">17</span></a></p><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Allergic Contact Dermatitis</span><p id="par0045" class="elsevierStylePara elsevierViewall">Gonzalez <span class="elsevierStyleItalic">et al&#46;</span> published the first study on ACD using RCM involving 5 patients with a clinical history of ACD&#46; This study aimed to investigate if the changes seen over time by histology can also be seen by RCM&#46; Patches containing nickel sulfate 5&#37;&#44; balsam of Peru 25&#37;&#44; and fragrance mix 8&#37; were placed for 24 and 48<span class="elsevierStyleHsp" style=""></span>hours prior to removal&#46; RCM images of reaction sites and adjacent skin were captured immediately&#44; and at 24&#44; 48&#44; and 72<span class="elsevierStyleHsp" style=""></span>hours post-patch removal&#46; RCM-pathologic comparison was made with hematoxylin-eosin &#40;H&#38;E&#41; staining of a 3<span class="elsevierStyleHsp" style=""></span>mm skin biopsy taken 24<span class="elsevierStyleHsp" style=""></span>hours after patch removal&#46; Immediately upon patch removal&#44; there were variably sized vesicles and exocytosis of lymphocytes and Langerhans cells&#44; but no observable SC disruption&#46; At 24<span class="elsevierStyleHsp" style=""></span>hours post-patch removal&#44; the SC remained intact but showed dendritic cells and parakeratosis&#46; The most relevant features at 48 and 72<span class="elsevierStyleHsp" style=""></span>hours post-patch removal included SC disruption&#44; spongiosis&#44; and at a depth of 56<span class="elsevierStyleHsp" style=""></span>&#956;m&#44; increased volume and diameter &#40;10-22<span class="elsevierStyleHsp" style=""></span>&#956;m&#41; of dermal vasculature when compared to untreated skin &#40;5-10<span class="elsevierStyleHsp" style=""></span>&#956;m&#41;&#46; These RCM features were consistently observed on H&#38;E-stained biopsy&#44; supporting the notion that RCM can be used as an adjunct diagnostic tool&#46; The authors mentioned that their study was limited by feature variability amongst the individuals and allergens&#44;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">18</span></a> thus studies are needed to explore whether each allergens can elicit unique RCM features&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Despite the promising correlations Gonzalez <span class="elsevierStyleItalic">et al&#46;</span> made between the ACD features on RCM and histopathology&#44; the sensitivity of RCM in detecting ACD remained unknown&#46; A pilot study by Astner <span class="elsevierStyleItalic">et al&#46;</span> investigated the sensitivity of RCM for ACD in 16 patients with a history of skin allergy&#46; Patches containing specific allergens and a phosphate-buffered saline solution control were placed for 48<span class="elsevierStyleHsp" style=""></span>hours prior to removal&#46; Clinical grading and RCM image grading was performed by three independent blinded observers using a presence-absence scheme&#59; the clinical grading was performed at 48 and 72<span class="elsevierStyleHsp" style=""></span>hours post-patch removal&#44; and the RCM images were captured at 72<span class="elsevierStyleHsp" style=""></span>hours post-patch removal&#46; RCM identified ACD reactions as having stratum spinosum spongiosis&#44; stratum granulosum spongiosis&#44; and exocytosis &#40;sensitivity 100&#37;&#44; 95&#46;8&#37;&#44; and 100&#37; respectively&#59; specificity 92&#46;6&#37;&#44; 96&#46;3&#37; and 74&#46;1&#37; respectively&#41;&#46; To offset the simplicity of the presence-absence schema&#44; logistic regression analysis indicated that the best predictor for ACD detection is the presence of stratum spinosum spongiosis&#44; which positively correlated with stratum granulosum and stratum spinosum vesicle formation&#44; stratum granulosum spongiosis&#44; and stratum spinosum and stratum granulosum inflammatory infiltrate&#46; Changes within the SC were the least sensitive for diagnosing ACD&#44; a finding which has been confirmed in subsequent studies&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">7</span></a> In one of the participants&#44; ACD from wool alcohols was detected by RCM at 72-hour post-patch removal when clinical evaluation was negative&#44; suggesting that RCM was more sensitive than clinical evaluation&#46; Three patients with borderline-positive clinical scores for their control sites had negative ACD changes on RCM&#44; suggesting that RCM can also identify false-positive patch reads&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">7</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Samhaber <span class="elsevierStyleItalic">et al&#46;</span> identified characteristic RCM features of vesiculobullous skin disorders&#44; including ACD&#46; In 12 patients with at least one unequivocal ACD reaction to a relevant allergen&#44; RCM images of 22 positive patch-induced ACD lesions were taken on day 3 or 4&#46; In line with earlier reports&#44; common RCM features were epidermal spongiosis&#44; increased vascularization&#44; and inflammatory infiltrate&#44; most prominent in the stratum spinosum and stratum granulosum&#46; In more severe reactions&#44; microvesicles&#47;vesicles were seen in 17 of the 22 patients within the stratum spinosum and stratum granulosum&#46; Parakeratosis was noted in 8 ACD lesions and was always associated with numerous microvesicle&#47;vesicles&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">19</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">To determine if there was a difference in allergic skin reaction from different reagents&#44; Sakanashi <span class="elsevierStyleItalic">et al&#46;</span> conducted a study involving 8 healthy volunteers and 11 patients with suspected contact allergy to dental metals&#46; Patches containing aqueous solutions of 5&#37; nickel sulfate &#40;Ni&#41; and 2&#37; cobalt chloride &#40;Co&#41; were applied for 48<span class="elsevierStyleHsp" style=""></span>hours&#46; Clinical grading and RCM imaging were captured at baseline&#44; and 20<span class="elsevierStyleHsp" style=""></span>minutes&#44; one day&#44; and five days post-patch removal&#46; Prior to PT&#44; there was no difference in suprabasal epidermal thickness between patients and healthy volunteers&#46; Ni- and Co-exposed skin on ACD patients had significantly increased suprabasal epidermal thickness compared to healthy volunteers at each time point evaluated&#44; when compared to baseline&#46; Notably&#44; this change was appreciated at 20<span class="elsevierStyleHsp" style=""></span>minutes following patch removal&#44; suggesting that RCM can detect very early ACD changes before they become visually apparent&#46; The Ni-positive group was further characterized by an overall increase in intercellular edema&#44; acanthosis&#44; and great vesicle formation&#44; suggesting that there are allergen-specific differences&#46; The authors postulate that Ni may induce a stronger keratinocyte proliferation response and T-cell recruitment&#46; Among doubtful-positive Co reactions &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#41;&#44; RCM images of two patients only showed superficial SC disruption&#44; and the third patient only had increased suprabasal epidermal thickness&#46; The authors believe that RCM helped to distinguish between doubtful-positive and negative ACD reactions&#44; which highlights the potential for RCM to precisely interpret true from doubtful ACD reactions&#46; Further&#44; this study suggest that various allergens may elicit different skin reactions that have distinct RCM features&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">20</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Irritant Contact Dermatitis</span><p id="par0065" class="elsevierStylePara elsevierViewall">Two studies attempted to distinguish the variability of ICD in opposing Fitzpatrick skin types using RCM and investigate if subclinical irritant reactions can be detected by RCM&#46; In a study by Astner <span class="elsevierStyleItalic">et al&#46;</span> involving 10 healthy Caucasians &#40;Fitzpatrick II&#47;III&#41; and 10 healthy African Americans &#40;AA&#44; Fitzpatrick V&#47;VI&#41;&#44; PT containing Ivory dishwashing liquid and distilled water as a negative control were placed for 24<span class="elsevierStyleHsp" style=""></span>hours&#46; Caucasians were exposed to 10&#37; threshold and 5&#37; subthreshold irritant solution&#44; while AA were exposed to 25&#37; threshold and 20&#37; subthreshold irritant solution&#46; Threshold was defined as the lowest irritant concentration to which a clinical reaction was detected&#44; whereas subthreshold was defined as the highest irritant concentration to which a skin reaction was not clinically appreciated&#46; The authors commented that the higher concentration needed to elicit erythema could either be due to difficulty in ascertaining erythema in deeply pigmented skin&#44; and&#47;or that AA skin is more durable when exposed to irritants&#46; Clinical scoring&#44; TEWL&#44; and RCM imaging were performed at 24-hour post-patch removal&#46; RCM features of ICD were observed in both groups of patients at threshold and subthreshold irritancy concentrations&#44; and included SC disruption&#44; parakeratosis&#44; individual corneocytes&#44; spongiosis&#44; and stratum granulosum and stratum spinosum vesicle formation&#46; RCM detected ICD features even when a visible clinical response was either absent or very subtle&#46; This suggests lower irritant concentrations may be sufficient to elicit detectable cutaneous responses for PT in conjunction with RCM&#46; On RCM analysis&#44; Caucasians experienced significantly more severe SC disruption&#44; epidermal spongiosis&#44; and parakeratosis than AA&#46; Caucasians also had dose-dependent TEWL increase&#44; even in the absence of a visible clinical reaction&#46; The authors further explained that AA&#39;s higher irritancy threshold and lower TEWL can be attributed to their increased number of SC cell layers and greater intercellular cohesiveness compared to Caucasian skin&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">21</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">In a study by Hicks <span class="elsevierStyleItalic">et al&#46;</span> involving 8 Fitzpatrick II&#47;III participants and 6 Fitzpatrick V&#47;VI participants&#44; PT containing 4&#37; SLS for 6<span class="elsevierStyleHsp" style=""></span>hours and 4&#37; SLS&#44; 1&#37; SLS&#44; and phosphate-buffered solution for 24<span class="elsevierStyleHsp" style=""></span>hours was performed&#46; Clinical evaluation&#44; TEWL measurements&#44; and RCM imaging were performed at 6&#44; 24&#44; and 48<span class="elsevierStyleHsp" style=""></span>hours after initial application&#46; In contrast to Astner <span class="elsevierStyleItalic">et al&#46;</span>&#8217;s ethnicity study&#44; AA had significantly less SC thickness than Caucasians&#44; but only detectable at 4&#37; SLS at 48<span class="elsevierStyleHsp" style=""></span>hours&#46; This suggests that AA may experience greater irritant-induced erosion compared to Caucasians&#46; This contests the previous findings that deeply pigmented SC is more densely layered&#44; as it is expected that thicker skin is less penetrable by SLS&#46; Additionally&#44; Caucasian&#39;s suprapapillary epidermal plate was thicker than that of AA when exposed to 4&#37; SLS at 24 and 48<span class="elsevierStyleHsp" style=""></span>hours&#44; and 1&#37; SLS at 48<span class="elsevierStyleHsp" style=""></span>hours&#46; This is possibly due to the more severe spongiosis and vesicle formation within the epidermis&#44; and may explain the more severe clinical reaction seen in Caucasians&#46; Interestingly&#44; in both groups&#44; positive RCM features were identified in exposed sites even when ICD reactions were not clinically evident&#46; This further suggests that RCM is more sensitive for detecting ICD reactions than clinical examination in both darkly and lightly pigmented individuals&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">22</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Vitamin E is an anti-oxidant that dampens irritation and stimulates repair mechanisms after irritation&#46; Thus&#44; Casari <span class="elsevierStyleItalic">et al&#46;</span> aimed to determine whether such an anti-oxidant can affect ICD reactions&#44; and if these changes could be identified through RCM&#46; Three patches containing SLS 5&#37; solution were placed on the volar forearm of 10 healthy subjects for 24<span class="elsevierStyleHsp" style=""></span>hours&#46; Vitamin E product &#40;10&#37; tocopherols&#44; 0&#46;3&#37; tocotrienols&#41; was applied at one site prior to SLS patch placement&#44; one site post-SLS patch placement&#44; and not at all at the third control site&#46; TEWL measurements and RCM imaging were performed immediately&#44; 30<span class="elsevierStyleHsp" style=""></span>minutes&#44; and 24<span class="elsevierStyleHsp" style=""></span>hours after patch-removal&#46; Immediately following patch removal&#44; TEWL increased at control sites&#46; At 48<span class="elsevierStyleHsp" style=""></span>hours&#44; vitamin E sites showed lower TEWL than the control sites&#46; At 24<span class="elsevierStyleHsp" style=""></span>hours there was significantly less detached corneocytes&#44; targetoid keratinocytes&#44; and irregular rings in the vitamin E area compared to control&#44; suggesting that vitamin E&#39;s protective effect on irritancy was detectable through RCM&#46; At 48<span class="elsevierStyleHsp" style=""></span>hours&#44; there were significantly less targetoid keratinocytes and irregular rings in the vitamin E compared to the control site&#46; The authors did not correlate RCM features with a clinical scoring system&#46; Nevertheless&#44; this study demonstrates the utility and potential that RCM holds in monitoring dynamic lesions&#44; especially those undergoing treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">23</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Comparing Allergic Contact Dermatitis and Irritant Contact Dermatitis</span><p id="par0080" class="elsevierStylePara elsevierViewall">With the shared and individual characteristics of ACD and ICD outlined in prior studies&#44; there was a need to determine whether RCM can accurately differentiate ACD from ICD&#46; Quaternary ammonium compounds &#40;Quats&#41; such as benzalkonium chloride &#40;BAC&#41; and benzathonium chloride &#40;BEC&#41; are known to elicit both allergic and irritant reactions&#44; making it difficult to identify the true pathogenesis&#46; Benjamin <span class="elsevierStyleItalic">et al&#46;</span> attempted to distinguish ACD and ICD reactions using RCM&#46; Eight subjects either with a history of prior positive PT to BAC &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#41;&#44; or a self-reported history of hand dermatitis after exposure to anti-bacterial skin products &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#41;&#44; and healthy controls &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#41; were enrolled&#46; Patch testing containing BACaq &#91;0&#46;15&#37; &#40;aqueous vehicle&#41;&#93;&#44; BACpet &#91;0&#46;15&#37; &#40;petrolatum vehicle&#41;&#93;&#44; BECaq &#40;0&#46;05&#37;&#41;&#44; BECpet &#40;0&#46;15&#37;&#41;&#44; BECaq &#40;0&#46;15&#37;&#41;&#44; BECaq &#40;0&#46;5&#37;&#41;&#44; SLSaq &#40;2&#37;&#41; positive irritant control&#44; and deionized water negative control were placed for 48<span class="elsevierStyleHsp" style=""></span>hours prior to removal&#46; Clinical grading and RCM imaging were performed on days 4 and 7 post-patch removal&#46; Similar to the findings in previous studies&#44; RCM features of ACD included SC disruption and parakeratosis&#44; microvesicle formation in the stratum granulosum&#44; stratum spinosum&#44; and dermo-epidermal junction&#46; Clinically positive reactions for BACaq 0&#46;15&#37; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#41; and BECaq 0&#46;15&#37; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#41; resulted in ACD characteristics that were noted on RCM analysis&#46; Positive clinical reactions for BECpet 0&#46;15&#37; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#41; were read as &#8216;subtle changes&#8217; on RCM&#59; clinically positive reactions from BECaq 0&#46;5&#37; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#41; were read as &#8220;possible&#8221; ACD&#46; There were no clinical reactions that resulted from exposure to BACpet 0&#46;15&#37; or BECaq 0&#46;05&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">24</span></a> Among the 10 patients who were exposed to SLSaq 2&#46;0&#37;&#44; 7 patients had positive clinical reactions&#44; with SC disruption&#44; parakeratosis&#44; and increased epidermal thickness on RCM analysis&#46; The data suggests that RCM can rectify that Quats are true allergens&#44; rather than irritants&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">24</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Another study by Astner <span class="elsevierStyleItalic">et al&#46;</span> compared clinical grading to combined technical evaluation methods &#91;RCM&#44; TEWL and fluorescent excitation spectroscopy &#40;FES&#41;&#93; in differentiating ACD and ICD<span class="elsevierStyleItalic">&#46;</span> Eighteen individuals with a history of ACD received two patches containing 4&#37; SLS&#44; a specific allergen&#44; a phosphate-buffered saline control&#44; and negative control&#46; Patches were removed 48<span class="elsevierStyleHsp" style=""></span>hours later&#44; and the participants returned at three or more time points &#40;2&#44; 3&#44; 4&#44; 9&#44; 14&#44; 21 days&#41; following patch removal&#46; At each visit&#44; clinical grading by two independent observers&#44; RCM evaluation&#44; and TEWL were performed&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">14</span></a> An FES excitation&#47;emission of 295&#47;345<span class="elsevierStyleHsp" style=""></span>nm corresponds to epidermal proliferation<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">25&#8211;28</span></a> and&#47;or increased cellular activity&#44;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">29</span></a> whereas an excitation band at 270<span class="elsevierStyleHsp" style=""></span>nm is consistent with inflammation&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">30</span></a> Significant stratum granulosum and stratum spinosum microvesicle formation&#44; but not SC changes&#44; peaked at 96-hours post-patch removal and persisted beyond the ninth day&#44; indicating ACD reactions are prolonged&#46; FES did not differ between ACD and control at either 278<span class="elsevierStyleHsp" style=""></span>nm or 298<span class="elsevierStyleHsp" style=""></span>nm&#44; thus FES alone cannot distinguish between ACD reaction or no reaction&#46; No significant correlation was observed between clinical scoring and TEWL measurements or RCM and TEWL&#44; but it is unclear if RCM corresponds to clinical scoring&#46; Despite insignificant correlation&#44; peak in TEWL&#44; a measure of SC disruption&#44; was delayed to the 4<span class="elsevierStyleSup">th</span> day post-patch removal&#46; This suggests that SC disruption occurs much later in ACD lesions when compared to ICD reactions&#46; It is possible that prior studies did not appreciate significant SC disruption in ACD lesions as readings were done within seven days&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">14</span></a> ICD reactions were detected by RCM within 48<span class="elsevierStyleHsp" style=""></span>hours of patch removal&#44; which is earlier than the identification of ACD reactions&#46; RCM features include SC disruption&#44; exocytosis&#44; spongiosis&#44; vesicle formation&#44; and epidermal necrosis&#46; In contrast to ACD&#44; ICD reaction sites had an increase in FES at 278<span class="elsevierStyleHsp" style=""></span>nm and 298<span class="elsevierStyleHsp" style=""></span>nm&#44; corresponding to increased inflammation&#44; epidermal proliferation&#44; and increased cellular activity&#44; which correlated with increased spongiosis&#44; parakeratosis&#44; and hyperkaratosis characteristics of irritant reactions&#46; It appears that FES can be used to detect presence of ICD reactions&#44; but not ACD&#46; Early reaction formation and resolution versus late reaction formation and resolution corresponds to ICD and ACD reactions by RCM&#44; respectively&#46; SC disruption&#44; as identified via RCM and increase in TEWL and FES&#44; is a key early structural change for irritant reactions that occur much later with allergen-exposure&#44; and helps to distinguish between the two dermatoses&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">14</span></a></p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">CONCLUSION</span><p id="par0090" class="elsevierStylePara elsevierViewall">RCM is emerging as a valid modality for diagnosing cutaneous malignancies and inflammatory dermatoses that&#44; in the past&#44; necessitated biopsy or patch testing&#46; RCM has a comparable sensitivity and specificity compared to patch testing for contact dermatitis &#40;92&#37; vs 85&#37; specificity and 82&#37; vs 85&#37; sensitive&#44; respectively&#41;&#46; When compared to histology&#44; RCM can identify SC disruption&#44; parakeratosis&#44; stratum spinosum spongiosis&#44; stratum granulosum spongiosis&#44; and exocytosis&#46; Multiple studies have shown RCM is effective at diagnosing ICD in both light- and dark-skinned patients&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Research has demonstrated that RCM can augment current PT diagnosis of CD&#46; RCM can detect sub-clinical ACD and ICD reactions&#46; It can help distinguish between doubtful-positive and negative ACD reactions&#46; RCM can detect pathological changes within minutes to a day when using patch testing&#46; This early reaction detection could change how PT is performed in the future&#46; RCM can be used to track dynamic changes in the skin&#44; such as treatment process and resolution&#46; It has been demonstrated that RCM can detect differences between ACD and ICD even when they appear morphologically similar&#44; helping distinguish these two entities&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Many of the RCM devices used in the studies herein were traditional RCM &#40;non-handheld&#41; devices&#46; These devices are limited by the imaging of curved skin surfaces on a live subject&#46; Lateral movement is controlled with the use of a tissue ring-and-window device attached to both the skin and device however&#44; breathing and minor movement create vertical motion artifact that may affect redundancy in stack image collection&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">31</span></a> Currently&#44; hand held confocal devices reduce technical limitations of traditional RCM devices&#46; Future generations of RCM devices can be improved to further address this technical limitation&#46; An additional limitation for RCM is the cost&#44; which is estimated to be 30&#44;000 USD&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">To date&#44; studies have identified RCM features that can detect subclinical reactions to differentiate morphologically similar lesions &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; Further studies should aim to examine the difference in ACD presentation in different Fitzpatrick types&#44; much like what has been done for ICD&#46; Studies are also needed to optimize RCM image protocol and laser settings that are most suitable for each condition&#44; anatomical location&#44; and Fitzpatrick skin type&#46; Pilot studies are needed to identify RCM features in other inflammatory dermatoses in order to compare features among various erythematosquamous conditions&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span></span>"
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          "titulo" => "INTRODUCTION"
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              "titulo" => "Contact Dermatoses"
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          "identificador" => "sec0015"
          "titulo" => "MATERIALS AND METHODS"
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          "titulo" => "REVIEW OF LITERATURE"
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              "titulo" => "Allergic Contact Dermatitis"
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              "identificador" => "sec0030"
              "titulo" => "Irritant Contact Dermatitis"
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            2 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "Comparing Allergic Contact Dermatitis and Irritant Contact Dermatitis"
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          "identificador" => "sec0040"
          "titulo" => "CONCLUSION"
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            0 => "Reflectance confocal microscopy"
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            2 => "Allergic contact dermatitis"
            3 => "Irritant contact dermatitis"
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            0 => "Microscopia confocal de reflectancia"
            1 => "Microscopia in vivo"
            2 => "Dermatitis al&#233;rgica de contacto"
            3 => "Dermatitis irritativa de contacto"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Dermatologic diagnosis and monitoring have been dependent largely on visual grading&#46; A skin biopsy is performed in case of diagnostic uncertainty&#44; but can be traumatic&#44; and results are delayed due to time for specimen transport and processing&#46; Biopsies also destroy specimens&#44; prohibiting lesion evolution monitoring&#46; In vivo reflectance confocal microscopy &#40;RCM&#41; offers a diagnostic alternative to skin biopsy&#46; RCM captures real-time&#44; high-resolution images&#44; and has been piloted for the evaluation of various dermatologic conditions&#46; Identification of unique RCM features may distinguish dermatoses with similar clinical morphologies&#46; Allergic contact dermatitis &#40;ACD&#41; and irritant contact dermatitis &#40;ICD&#41; are diagnosed by patch testing that currently uses a subjective scoring system&#46; RCM has increasingly been studied for early detection and severity grading of CD&#46; Common RCM features shared by ACD and ICD are stratum corneum disruption&#44; vesicle formation&#44; exocytosis&#44; spongiosis&#44; and parakeratosis&#46; Features unique to ACD are vasodilation&#44; increased epidermal thickness&#44; intercellular edema&#44; and acanthosis&#46; Features unique to ICD are detached corneocytes and targetoid keratinocytes&#46; This review summarizes the use of RCM in evaluating contact eccematous conditions and aims to spark future research and interest in this promising tool&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Tanto el diagn&#243;stico como el seguimiento en la dermatolog&#237;a depender&#225;n en gran medida de una evaluaci&#243;n visual&#46; Cuando no se puede llegar al diagn&#243;stico&#44; se procede a realizar una biopsia cut&#225;nea&#44; un procedimiento invasivo y que con frecuencia los resultados retrasan debido a la demora del transporte&#44; as&#237; como al procesamiento de la muestra&#46; Por otro lado&#44; las biopsias pueden destruir las lesiones&#44; lo que imposibilitar&#225; realizar un seguimiento cl&#237;nico de la evoluci&#243;n de la lesi&#243;n a estudio&#46; La microscopia confocal de reflectancia in vivo &#40;MCR&#41; ofrece una alternativa diagn&#243;stica a la biopsia cut&#225;nea&#46; Esta t&#233;cnica captura en tiempo real im&#225;genes de alta resoluci&#243;n y se utilizar&#225; en la evaluaci&#243;n de diversas condiciones dermatol&#243;gicas&#46; La identificaci&#243;n de caracter&#237;sticas espec&#237;ficas en la MCR podr&#237;a ayudar a diferenciar dermatosis con una morfolog&#237;a cl&#237;nica similar&#46; La dermatitis al&#233;rgica de contacto &#40;DAC&#41; y la dermatitis irritativa de contacto &#40;DIC&#41; se diagnostican generalmente gracias a pruebas epicut&#225;neas&#59; estas&#44; a su vez&#44; se basar&#225;n en un sistema de valoraci&#243;n subjetiva&#46; El uso de la MCR tanto en la detecci&#243;n temprana&#44; como en la clasificaci&#243;n de la intensidad de la DC&#44; ha sido estudiado en m&#250;ltiples estudios&#46; Existir&#225;n algunas caracter&#237;sticas comunes en la MCR de la DAC como de la DIC&#46; Entre estas podemos se&#241;alar la disrupci&#243;n del estrato c&#243;rneo&#44; la formaci&#243;n de ves&#237;culas&#44; la exocitosis&#44; la espongiosis y la paraqueratosis&#46; Las caracter&#237;sticas espec&#237;ficas para la DAC ser&#225;n la presencia de vasodilataci&#243;n&#44; el aumento del grosor epid&#233;rmico&#44; edema intercelular y acantosis&#46; Las caracter&#237;sticas espec&#237;ficas de la DIC son la presencia de los corneocitos disgregados y queratinocitos en diana&#46; Esta revisi&#243;n resume la utilidad de la MCR en las condiciones eccematosas de contacto cut&#225;neas y busca incentivar futuras investigaciones&#44; as&#237; como incrementar el inter&#233;s cl&#237;nico en esta prometedora t&#233;cnica&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58;&#46;</p>"
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      1 => array:1 [
        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">&#46; Microscopia confocal de reflectancia in vivo&#58; papel emergente en el diagn&#243;stico no invasivo&#44; as&#237; como en el seguimiento de las dermatosis eccematosas Actas Dermosifiliogr&#46; 2019&#59;110&#58;626&#8211;636&#46;</p>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A A low power &#40;&#60;30 mW&#41;&#44; tissue-sparing laser includes a laser light source&#44; scanning elements&#44; relay telescope&#44; beam splitter&#44; pinhole aperture&#44; objective lens&#44; and detector to generate images of dark and bright cutaneous structures&#46;</p> <p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Figure 1B&#58; Representative stacking of imaging&#44; revealing characteristics from the epidermis to the upper reticular dermis&#46;</p>"
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">A Allergic Contact Dermatitis&#58; Reflectance confocal microscopy image &#40;0&#46;5<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>0&#46;5<span class="elsevierStyleHsp" style=""></span>mm&#41; at the level of the spinous layer &#40;&#8764;30 microns depth&#41; shows spongiosis and exocytosis &#40;yellow arrow&#41; and multiple microvesicles with lymphocytes and detached keratinocytes &#40;red arrow&#41;&#46;</p> <p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Figure 2B&#58; Irritant contact dermatitis&#58; Reflectance confocal microscopy image &#40;0&#46;5<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>0&#46;5<span class="elsevierStyleHsp" style=""></span>mm&#41; shows disruption of stratum corneum with detached corneocytes and early parakeratosis &#40;yellow arrows&#41; and confluence of microvesicles with inflammatory cells infiltration &#40;red arrow&#41; below&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Morphology&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">No rxn&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Negative rxn&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">&#63;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Faint erythema only&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Doubtful rxn&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Erythema&#44; infiltration&#44; possibly papules&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Weak positive rxn&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">Erythema&#44; infiltration&#44; papules&#44; vesicles&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Strong positive rxn&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">Intense erythema&#44; infiltrate&#44; coalescing vesicles&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">Extreme positive rxn&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">IR&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Various morphologies&#44; eg&#46; bulla&#44; necrosis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Irritant rxn&#46;&nbsp;\t\t\t\t\t\t\n
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          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; RCM&#58; Reflectance Confocal Microscopy&#59; CD&#58; Contact Dermatitis&#59; ACD&#58; Allergic Contact Dermatitis&#59; SC&#58; Stratum Corneum&#59; SS&#58; Stratum Spinosum&#59; SG&#58; Stratum Granulosum&#59; ICD&#58; Irritant Contact Dermatitis&#59; SLS&#58; Sodium Lauryl Sulfate</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Reference&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Condition&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patient &#40;N&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Allergens&#47; Irritants Used&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">RCM Features&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Koller <span class="elsevierStyleItalic">et al&#46;</span><a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">17</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Unspecified CD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20 CD lesions and 10 healthy controls&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Not mentioned&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RCM detected CD with 83&#37; sensitivity and 92&#37; specificityExocytosisEpidermal edemaDermal vasodilatationIntraepidermal vesicle formation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Gonzalez <span class="elsevierStyleItalic">et al&#46;</span><a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">18</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ACD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nickel sulfate 5&#37;&#44; Balsam of Peru 25&#37;&#44; and Fragrance mix 8&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Immediate patch removal&#58;VesiclesExocytosis of lymphocytes and Langerhans cells24<span class="elsevierStyleHsp" style=""></span>hours post patch removal&#58;Dendritic cellsParakeratosis48 and 72<span class="elsevierStyleHsp" style=""></span>hours post patch removal&#58;SC disruptionSpongiosisIncreased volume and diameter of dermal vasculature&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Astner <span class="elsevierStyleItalic">et al&#46;</span><a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">7</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ACD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8220;Specific allergen&#8221;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SC disruptionParakeratosisSS spongiosis &#40;sensitivity 100&#37;&#44; specificity 93&#37;&#41;SG spongiosis &#40;sensitivity 96&#37;&#44; specificity 96&#37;&#41;Exocytosis &#40;sensitivity 100&#37;&#44; specificity 74&#37;&#41;SS and SG vesicle formationSS and SG inflammatory infiltrate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Samhaber <span class="elsevierStyleItalic">et al&#46;</span><a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">19</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ACD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8220;Relevant allergen&#8221;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Epidermal spongiosisIncreased vascularizationSS and SG inflammatory infiltrateSS and SG microvesicles&#47;vesiclesParakeratosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sakanashi <span class="elsevierStyleItalic">et al&#46;</span><a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">20</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ACD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11 volunteers with contact allergy and 8 healthy volunteers&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#37; nickel sulfate and 2&#37; cobalt chloride&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Increased suprabasal epidermal thicknessIntercellular edemaAcanthosisGreat vesicle formation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Astner <span class="elsevierStyleItalic">et al&#46;</span><a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">21</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ICD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 Caucasians and 10 healthy AA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Caucasians&#58; 10&#37; &#40;threshold&#41; and 5&#37; &#40;subthreshold&#41; irritant solutionAA&#58; 25&#37; &#40;threshold&#41; and 20&#37; &#40;subthreahold&#41; irritant solution&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SC disruptionParakeratosisCorneocytesSpongiosisSS and SG vesicle formation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hicks <span class="elsevierStyleItalic">et al&#46;</span><a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">22</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ICD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 Caucasians and 6 healthy AA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#37; SLS&#44; 4&#37; SLS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SpongiosisVesicle formationSC disruptionFocal parakeratosisExocytosisMicrovesicles containing inflammatory cells and detached keratinocytesPerivascular inflammatory infiltrate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Casari <span class="elsevierStyleItalic">et al&#46;</span><a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">23</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ICD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#37; SLS &#40;Observed difference in RCM features following Vitamin E product application&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Compared to control&#44; Vitamin E reduced the concentration of&#58;Detached corneocytesTargetoid and bright keratinocytes &#40;necrotic&#47;apoptotic cells&#41;Irregular keratinocyte architecture in the SS and SGIrregular rings in the DEJ&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Benjamin <span class="elsevierStyleItalic">et al&#46;</span><a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">24</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ACD and ICD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;15&#37; BACaq&#44; 0&#46;15&#37; BACpet&#44; 0&#46;05&#37; BECaq&#44; 0&#46;15&#37; BECpet&#44; 0&#46;15&#37; BECaq&#44; 0&#46;5&#37; BECaq&#44; 2&#37; SLSaq&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ACDSC disruption and parakeratosisMicrovesicle formation in the SS&#44; SG&#44; and DEJICDSC disruption and parakeratosisIncreased epidermal thickness&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Astner <span class="elsevierStyleItalic">et al&#46;</span><a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">32</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ACD and ICD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#37; SLS and a specific allergen&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ACD &#91;Delayed and prolonged &#40;96<span class="elsevierStyleHsp" style=""></span>hours post-patch removal&#41;&#93;SG and SS microvesicle formationICD &#91;Early &#40;within 48<span class="elsevierStyleHsp" style=""></span>hours post-patch removal&#41;&#93;SC disruptionExocytosisSpongiosisVesicle formationEpidermal necrosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Summary of Reviewed Studies Evaluating RCM Features in ACD and ICD&#46;</p>"
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        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
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            "identificador" => "at3"
            "detalle" => "Table "
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        "tabla" => array:1 [
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            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ACD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ICD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Disruption of SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Spongiosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X &#40;particularly of SS&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Parakeratosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vesicle formation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X &#40;microvesicles&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Exocytosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Inflammatory cell infiltrate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vasodilation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Epidermal thickness&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Intercellular edema&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Acanthosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Detached corneocytes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Targetoid keratinocytes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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              "imagenFichero" => array:1 [
                0 => "xTab2142228.png"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Summary of Reported RCM Features in ACD and ICD&#46;</p>"
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                        0 => array:2 [
                          "etal" => false
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                      "Revista" => array:5 [
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                      "titulo" => "Reflectance confocal microscopy&#58; An overview of technology and advances in telepathology"
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                      "doi" => "10.1016/j.jaad.2005.08.026"
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                      "titulo" => "The cost of occupational skin disease"
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                      "Revista" => array:6 [
                        "tituloSerie" => "Arch Dermatol&#46;"
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                      "titulo" => "Contact dermatitis&#58; Allergic and irritant"
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                          "etal" => false
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                            0 => "C&#46;H&#46; Tan"
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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
M. Maaroufa, C.M. Costellob, S. Gonzalezc, I. Angulod, C.N. Curiel-Lewandrowskie, V.Y. Shie,
Corresponding author
vshi@email.arizona.edu

Corresponding author.
a Facultad de Medicina, Universidad de Arizona, Tucson, Arizona, Estados Unidos
b Departamento de Dermatología, Clínica Mayo, Scottsdale, Arizona, Estados Unidos
c Servicio de Dermatología, Hospital Ramón y Cajal, Universidad de Alcalá, Madrid, España
d Departamento de Medicina, Universidad de Arizona, Tucson, Arizona, Estados Unidos
e División de Dermatología, Departamento de Medicina, Universidad de Arizona, Tucson, Arizona, Estados Unidos
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">A Allergic Contact Dermatitis&#58; Reflectance confocal microscopy image &#40;0&#46;5<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>0&#46;5<span class="elsevierStyleHsp" style=""></span>mm&#41; at the level of the spinous layer &#40;&#8764;30 microns depth&#41; shows spongiosis and exocytosis &#40;yellow arrow&#41; and multiple microvesicles with lymphocytes and detached keratinocytes &#40;red arrow&#41;&#46;</p> <p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Figure 2B&#58; Irritant contact dermatitis&#58; Reflectance confocal microscopy image &#40;0&#46;5<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>0&#46;5<span class="elsevierStyleHsp" style=""></span>mm&#41; shows disruption of stratum corneum with detached corneocytes and early parakeratosis &#40;yellow arrows&#41; and confluence of microvesicles with inflammatory cells infiltration &#40;red arrow&#41; below&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">INTRODUCTION</span><p id="par0005" class="elsevierStylePara elsevierViewall">In Vivo Reflectance Confocal Microscopy &#40;RCM&#41; is a non-invasive technique that captures live&#44; instantaneous&#44; high-resolution images of skin&#39;s ultrastructure&#46; In 1957&#44; mathematician and computer scientist Marvin Minksy patented the first confocal microscope for brain tissue imaging&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">1</span></a> RCM was later used for nuclear and cellular visualization of human skin by Rajadhyaksha and colleagues in 1995&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">2</span></a> From the late 1990s to 2010&#44; published literature on RCM for dermatologic evaluations has increased by 20-fold&#44; demonstrating the potential that RCM holds in dermatology&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">RCM utilizes a low power &#40;&#60;30 mW&#41;&#44; tissue-sparing laser to capture real-time ultrastructural images that span the epidermis to the upper reticular dermis &#40;up to 350<span class="elsevierStyleHsp" style=""></span>&#956;m depth&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">4</span></a> The commercial microscope includes laser light source &#40;single laser&#58; 830<span class="elsevierStyleHsp" style=""></span>nm&#44; or multi-laser&#58; 488<span class="elsevierStyleHsp" style=""></span>nm&#44; 658<span class="elsevierStyleHsp" style=""></span>nm&#44; 785<span class="elsevierStyleHsp" style=""></span>nm&#41;&#44; scanning elements&#44; relay telescope&#44; beam splitter&#44; pinhole aperture&#44; objective lens&#44; and detector &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>A&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">4&#44;5</span></a> When the light beam illuminates the skin&#44; differences in refractance generate images of dark &#40;non-reflecting&#41; and bright &#40;reflecting&#41; structures within seconds&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">4</span></a> This corresponds to a boundary between two separate cellular structures that have different indices of refraction&#44; including&#44; but not limited to membranes&#44; inflammatory debris&#44; and melanosomes&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">4</span></a> Light is reflected back towards an objective lens&#46; Prior&#44; a pinhole aperture filters out scattered light to create a high-resolution image similar to conventional histology&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">4&#44;5</span></a> Each image collected is viewed in a 500<span class="elsevierStyleHsp" style=""></span>&#956;m<span class="elsevierStyleSup">2</span> &#8211; 8<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleSup">2</span> field of view with 30X magnification&#46; The device captures multiple images in two-dimensions with horizontal image stacking &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>B&#41;&#44; which differs from vertical sectioning of standard histopathology&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">5</span></a> Single laser RCM devices are handheld&#44; conferring ease of use&#46; Multi-laser devices combine fluorescent light spectrum microscopy and RCM&#46; Fluorescent light spectrum microscopy augments the wavelength spectrum to identify more features of normal and pathologic skin&#46; RCM has some advantages over dermoscopy as it can magnify cellular structures and features unique to each skin layer&#44; and collect time-lapse photography to allow detection of dynamic skin changes&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">6</span></a> Additionally&#44; detection of subclinical changes by RCM allows for early treatment implementation and prevents premature treatment termination&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">7</span></a> RCM imaging may also reduce participation commitment for both patients and clinicians&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">8</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Contact Dermatoses</span><p id="par0015" class="elsevierStylePara elsevierViewall">Approximately 20&#37; of the U&#46;S&#46; population is affected by contact dermatitis &#40;CD&#41;&#44; which account for up to 95&#37; of occupational dermatoses&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">9</span></a> Allergic contact dermatitis &#40;ACD&#41; occurs when contact with a particular substance elicits a delayed Type-IV hypersensitivity reaction that necessitates a 10-14 day sensitization phase&#46; Upon allergen re-exposure&#44; the reaction develops within 24-48<span class="elsevierStyleHsp" style=""></span>hours&#46; ACD manifests as pruritic&#44; erythematous&#44; scaly&#44; edematous plaques with vesiculation at the sites of exposure&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">10</span></a> Histologically&#44; ACD presents with vesicle formation&#44; inflammatory infiltrate&#44; and spongiosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">11&#8211;13</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Whereas ACD requires prior exposure to elicit a cutaneous response&#44; irritant contact dermatitis &#40;ICD&#41; can result from a singular exposure to an irritant&#46; ICD presents with erythema&#44; fissuring&#44; and xerosis&#44; typically with more burning and less itching than ACD&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">10</span></a> Histologically&#44; ICD causes significant stratum corneum &#40;SC&#41; disruption&#44; parakeratosis&#44; and increased epidermal thickness&#46; Despite differences in patho-etiology&#44; ACD and ICD may have similar morphology&#44; and are often difficult to distinguish based on visual inspection alone&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">14</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Patch testing &#40;PT&#41; is the current gold standard to elicit CD&#44; followed by clinician interpretation using the International Contact Dermatitis Research Group scoring system &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; The scoring system has a sensitivity and specificity of 85&#37;&#44; with a 15-18&#37; false-positive rate&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">15</span></a> Evaluation of cutaneous reactions is highly subjected to inter- and intra-grader variability&#46; It is important to note that the same criteria are used for diagnosing both ACD and ICD&#44; with no standardized parameter to differentiate the two&#46; Thus&#44; there is a practical need to provide more consistent and objective grading in CD&#46; <a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">RCM has been used to distinguish eczematous conditions with similar morphologies&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">4</span></a> Early reaction detection by RCM may reduce the need for subsequent visits to grade delayed hypersensitivity reactions&#44; and allow for early treatment implementation&#46; In 2015&#44; Hoogedoorn et al&#46; briefly discussed ACD and ICD in their systematic review of the RCM literature on inflammatory skin diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">16</span></a> Our updated in-depth review summarizes current evidence on the emerging use of RCM for diagnosis and monitoring of contact eczematous conditions&#44; including ACD and ICD&#46;</p></span></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">MATERIALS AND METHODS</span><p id="par0035" class="elsevierStylePara elsevierViewall">In October 2017&#44; two research personnel conducted a literature review to explore established RCM features of CD&#46; PubMed and Google Scholar websites were searched using the terms &#8216;reflectance confocal microscopy&#8217; AND &#8216;eczematous dermatoses&#44;&#8217; OR &#8216;dermatitis&#44;&#8217; OR &#8216;allergic contact dermatitis&#44;&#8217; OR &#8216;irritant contact dermatitis&#46;&#8217; These search parameters yielded a total of 49 papers&#46; Literature selection was limited by publications or translations in the English language and randomized controlled trials &#40;RCT&#41;&#46; Three publications were excluded due to their primary discussion of laser scanning microscopy or fluorescence confocal microscopy&#46; The 10 studies included in this review involved the use of RCM in RCT&#44; and are summarized in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">REVIEW OF LITERATURE</span><p id="par0040" class="elsevierStylePara elsevierViewall">Koller <span class="elsevierStyleItalic">et al</span>&#46; evaluated the validity of RCM in diagnosing CD&#46; Twenty CD lesions and 10 healthy tissue controls were confirmed by histology &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9&#41; or positive PT &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41;&#44; and verified by three independent dermatologists who had moderate RCM grading experience&#46; RCM detected CD with 83&#37; sensitivity and 92&#37; specificity and healthy skin with 97&#37; sensitivity and 99&#37; specificity&#46; The authors attributed these statistical differences to more complex morphologic features in CD&#46; Features present in CD RCM images were exocytosis&#44; epidermal edema&#44; and dermal vasodilatation&#46; Intraepidermal vesicle formation in the upper epidermis and dermo-epidermal junction had high inter-observer agreement&#46; When using these two features alone&#44; classification tree software analysis accurately identified 82&#37; of CD lesions&#46; However&#44; with only 20 CD lesions analyzed&#44; it&#39;s unclear if these findings can be generalized to the overall population&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">17</span></a> The authors made no distinction between ACD and ICD&#46; Nevertheless&#44; the findings offer potential for further exploration comparing ACD and ICD reactions&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">17</span></a></p><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Allergic Contact Dermatitis</span><p id="par0045" class="elsevierStylePara elsevierViewall">Gonzalez <span class="elsevierStyleItalic">et al&#46;</span> published the first study on ACD using RCM involving 5 patients with a clinical history of ACD&#46; This study aimed to investigate if the changes seen over time by histology can also be seen by RCM&#46; Patches containing nickel sulfate 5&#37;&#44; balsam of Peru 25&#37;&#44; and fragrance mix 8&#37; were placed for 24 and 48<span class="elsevierStyleHsp" style=""></span>hours prior to removal&#46; RCM images of reaction sites and adjacent skin were captured immediately&#44; and at 24&#44; 48&#44; and 72<span class="elsevierStyleHsp" style=""></span>hours post-patch removal&#46; RCM-pathologic comparison was made with hematoxylin-eosin &#40;H&#38;E&#41; staining of a 3<span class="elsevierStyleHsp" style=""></span>mm skin biopsy taken 24<span class="elsevierStyleHsp" style=""></span>hours after patch removal&#46; Immediately upon patch removal&#44; there were variably sized vesicles and exocytosis of lymphocytes and Langerhans cells&#44; but no observable SC disruption&#46; At 24<span class="elsevierStyleHsp" style=""></span>hours post-patch removal&#44; the SC remained intact but showed dendritic cells and parakeratosis&#46; The most relevant features at 48 and 72<span class="elsevierStyleHsp" style=""></span>hours post-patch removal included SC disruption&#44; spongiosis&#44; and at a depth of 56<span class="elsevierStyleHsp" style=""></span>&#956;m&#44; increased volume and diameter &#40;10-22<span class="elsevierStyleHsp" style=""></span>&#956;m&#41; of dermal vasculature when compared to untreated skin &#40;5-10<span class="elsevierStyleHsp" style=""></span>&#956;m&#41;&#46; These RCM features were consistently observed on H&#38;E-stained biopsy&#44; supporting the notion that RCM can be used as an adjunct diagnostic tool&#46; The authors mentioned that their study was limited by feature variability amongst the individuals and allergens&#44;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">18</span></a> thus studies are needed to explore whether each allergens can elicit unique RCM features&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Despite the promising correlations Gonzalez <span class="elsevierStyleItalic">et al&#46;</span> made between the ACD features on RCM and histopathology&#44; the sensitivity of RCM in detecting ACD remained unknown&#46; A pilot study by Astner <span class="elsevierStyleItalic">et al&#46;</span> investigated the sensitivity of RCM for ACD in 16 patients with a history of skin allergy&#46; Patches containing specific allergens and a phosphate-buffered saline solution control were placed for 48<span class="elsevierStyleHsp" style=""></span>hours prior to removal&#46; Clinical grading and RCM image grading was performed by three independent blinded observers using a presence-absence scheme&#59; the clinical grading was performed at 48 and 72<span class="elsevierStyleHsp" style=""></span>hours post-patch removal&#44; and the RCM images were captured at 72<span class="elsevierStyleHsp" style=""></span>hours post-patch removal&#46; RCM identified ACD reactions as having stratum spinosum spongiosis&#44; stratum granulosum spongiosis&#44; and exocytosis &#40;sensitivity 100&#37;&#44; 95&#46;8&#37;&#44; and 100&#37; respectively&#59; specificity 92&#46;6&#37;&#44; 96&#46;3&#37; and 74&#46;1&#37; respectively&#41;&#46; To offset the simplicity of the presence-absence schema&#44; logistic regression analysis indicated that the best predictor for ACD detection is the presence of stratum spinosum spongiosis&#44; which positively correlated with stratum granulosum and stratum spinosum vesicle formation&#44; stratum granulosum spongiosis&#44; and stratum spinosum and stratum granulosum inflammatory infiltrate&#46; Changes within the SC were the least sensitive for diagnosing ACD&#44; a finding which has been confirmed in subsequent studies&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">7</span></a> In one of the participants&#44; ACD from wool alcohols was detected by RCM at 72-hour post-patch removal when clinical evaluation was negative&#44; suggesting that RCM was more sensitive than clinical evaluation&#46; Three patients with borderline-positive clinical scores for their control sites had negative ACD changes on RCM&#44; suggesting that RCM can also identify false-positive patch reads&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">7</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Samhaber <span class="elsevierStyleItalic">et al&#46;</span> identified characteristic RCM features of vesiculobullous skin disorders&#44; including ACD&#46; In 12 patients with at least one unequivocal ACD reaction to a relevant allergen&#44; RCM images of 22 positive patch-induced ACD lesions were taken on day 3 or 4&#46; In line with earlier reports&#44; common RCM features were epidermal spongiosis&#44; increased vascularization&#44; and inflammatory infiltrate&#44; most prominent in the stratum spinosum and stratum granulosum&#46; In more severe reactions&#44; microvesicles&#47;vesicles were seen in 17 of the 22 patients within the stratum spinosum and stratum granulosum&#46; Parakeratosis was noted in 8 ACD lesions and was always associated with numerous microvesicle&#47;vesicles&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">19</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">To determine if there was a difference in allergic skin reaction from different reagents&#44; Sakanashi <span class="elsevierStyleItalic">et al&#46;</span> conducted a study involving 8 healthy volunteers and 11 patients with suspected contact allergy to dental metals&#46; Patches containing aqueous solutions of 5&#37; nickel sulfate &#40;Ni&#41; and 2&#37; cobalt chloride &#40;Co&#41; were applied for 48<span class="elsevierStyleHsp" style=""></span>hours&#46; Clinical grading and RCM imaging were captured at baseline&#44; and 20<span class="elsevierStyleHsp" style=""></span>minutes&#44; one day&#44; and five days post-patch removal&#46; Prior to PT&#44; there was no difference in suprabasal epidermal thickness between patients and healthy volunteers&#46; Ni- and Co-exposed skin on ACD patients had significantly increased suprabasal epidermal thickness compared to healthy volunteers at each time point evaluated&#44; when compared to baseline&#46; Notably&#44; this change was appreciated at 20<span class="elsevierStyleHsp" style=""></span>minutes following patch removal&#44; suggesting that RCM can detect very early ACD changes before they become visually apparent&#46; The Ni-positive group was further characterized by an overall increase in intercellular edema&#44; acanthosis&#44; and great vesicle formation&#44; suggesting that there are allergen-specific differences&#46; The authors postulate that Ni may induce a stronger keratinocyte proliferation response and T-cell recruitment&#46; Among doubtful-positive Co reactions &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#41;&#44; RCM images of two patients only showed superficial SC disruption&#44; and the third patient only had increased suprabasal epidermal thickness&#46; The authors believe that RCM helped to distinguish between doubtful-positive and negative ACD reactions&#44; which highlights the potential for RCM to precisely interpret true from doubtful ACD reactions&#46; Further&#44; this study suggest that various allergens may elicit different skin reactions that have distinct RCM features&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">20</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Irritant Contact Dermatitis</span><p id="par0065" class="elsevierStylePara elsevierViewall">Two studies attempted to distinguish the variability of ICD in opposing Fitzpatrick skin types using RCM and investigate if subclinical irritant reactions can be detected by RCM&#46; In a study by Astner <span class="elsevierStyleItalic">et al&#46;</span> involving 10 healthy Caucasians &#40;Fitzpatrick II&#47;III&#41; and 10 healthy African Americans &#40;AA&#44; Fitzpatrick V&#47;VI&#41;&#44; PT containing Ivory dishwashing liquid and distilled water as a negative control were placed for 24<span class="elsevierStyleHsp" style=""></span>hours&#46; Caucasians were exposed to 10&#37; threshold and 5&#37; subthreshold irritant solution&#44; while AA were exposed to 25&#37; threshold and 20&#37; subthreshold irritant solution&#46; Threshold was defined as the lowest irritant concentration to which a clinical reaction was detected&#44; whereas subthreshold was defined as the highest irritant concentration to which a skin reaction was not clinically appreciated&#46; The authors commented that the higher concentration needed to elicit erythema could either be due to difficulty in ascertaining erythema in deeply pigmented skin&#44; and&#47;or that AA skin is more durable when exposed to irritants&#46; Clinical scoring&#44; TEWL&#44; and RCM imaging were performed at 24-hour post-patch removal&#46; RCM features of ICD were observed in both groups of patients at threshold and subthreshold irritancy concentrations&#44; and included SC disruption&#44; parakeratosis&#44; individual corneocytes&#44; spongiosis&#44; and stratum granulosum and stratum spinosum vesicle formation&#46; RCM detected ICD features even when a visible clinical response was either absent or very subtle&#46; This suggests lower irritant concentrations may be sufficient to elicit detectable cutaneous responses for PT in conjunction with RCM&#46; On RCM analysis&#44; Caucasians experienced significantly more severe SC disruption&#44; epidermal spongiosis&#44; and parakeratosis than AA&#46; Caucasians also had dose-dependent TEWL increase&#44; even in the absence of a visible clinical reaction&#46; The authors further explained that AA&#39;s higher irritancy threshold and lower TEWL can be attributed to their increased number of SC cell layers and greater intercellular cohesiveness compared to Caucasian skin&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">21</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">In a study by Hicks <span class="elsevierStyleItalic">et al&#46;</span> involving 8 Fitzpatrick II&#47;III participants and 6 Fitzpatrick V&#47;VI participants&#44; PT containing 4&#37; SLS for 6<span class="elsevierStyleHsp" style=""></span>hours and 4&#37; SLS&#44; 1&#37; SLS&#44; and phosphate-buffered solution for 24<span class="elsevierStyleHsp" style=""></span>hours was performed&#46; Clinical evaluation&#44; TEWL measurements&#44; and RCM imaging were performed at 6&#44; 24&#44; and 48<span class="elsevierStyleHsp" style=""></span>hours after initial application&#46; In contrast to Astner <span class="elsevierStyleItalic">et al&#46;</span>&#8217;s ethnicity study&#44; AA had significantly less SC thickness than Caucasians&#44; but only detectable at 4&#37; SLS at 48<span class="elsevierStyleHsp" style=""></span>hours&#46; This suggests that AA may experience greater irritant-induced erosion compared to Caucasians&#46; This contests the previous findings that deeply pigmented SC is more densely layered&#44; as it is expected that thicker skin is less penetrable by SLS&#46; Additionally&#44; Caucasian&#39;s suprapapillary epidermal plate was thicker than that of AA when exposed to 4&#37; SLS at 24 and 48<span class="elsevierStyleHsp" style=""></span>hours&#44; and 1&#37; SLS at 48<span class="elsevierStyleHsp" style=""></span>hours&#46; This is possibly due to the more severe spongiosis and vesicle formation within the epidermis&#44; and may explain the more severe clinical reaction seen in Caucasians&#46; Interestingly&#44; in both groups&#44; positive RCM features were identified in exposed sites even when ICD reactions were not clinically evident&#46; This further suggests that RCM is more sensitive for detecting ICD reactions than clinical examination in both darkly and lightly pigmented individuals&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">22</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Vitamin E is an anti-oxidant that dampens irritation and stimulates repair mechanisms after irritation&#46; Thus&#44; Casari <span class="elsevierStyleItalic">et al&#46;</span> aimed to determine whether such an anti-oxidant can affect ICD reactions&#44; and if these changes could be identified through RCM&#46; Three patches containing SLS 5&#37; solution were placed on the volar forearm of 10 healthy subjects for 24<span class="elsevierStyleHsp" style=""></span>hours&#46; Vitamin E product &#40;10&#37; tocopherols&#44; 0&#46;3&#37; tocotrienols&#41; was applied at one site prior to SLS patch placement&#44; one site post-SLS patch placement&#44; and not at all at the third control site&#46; TEWL measurements and RCM imaging were performed immediately&#44; 30<span class="elsevierStyleHsp" style=""></span>minutes&#44; and 24<span class="elsevierStyleHsp" style=""></span>hours after patch-removal&#46; Immediately following patch removal&#44; TEWL increased at control sites&#46; At 48<span class="elsevierStyleHsp" style=""></span>hours&#44; vitamin E sites showed lower TEWL than the control sites&#46; At 24<span class="elsevierStyleHsp" style=""></span>hours there was significantly less detached corneocytes&#44; targetoid keratinocytes&#44; and irregular rings in the vitamin E area compared to control&#44; suggesting that vitamin E&#39;s protective effect on irritancy was detectable through RCM&#46; At 48<span class="elsevierStyleHsp" style=""></span>hours&#44; there were significantly less targetoid keratinocytes and irregular rings in the vitamin E compared to the control site&#46; The authors did not correlate RCM features with a clinical scoring system&#46; Nevertheless&#44; this study demonstrates the utility and potential that RCM holds in monitoring dynamic lesions&#44; especially those undergoing treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">23</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Comparing Allergic Contact Dermatitis and Irritant Contact Dermatitis</span><p id="par0080" class="elsevierStylePara elsevierViewall">With the shared and individual characteristics of ACD and ICD outlined in prior studies&#44; there was a need to determine whether RCM can accurately differentiate ACD from ICD&#46; Quaternary ammonium compounds &#40;Quats&#41; such as benzalkonium chloride &#40;BAC&#41; and benzathonium chloride &#40;BEC&#41; are known to elicit both allergic and irritant reactions&#44; making it difficult to identify the true pathogenesis&#46; Benjamin <span class="elsevierStyleItalic">et al&#46;</span> attempted to distinguish ACD and ICD reactions using RCM&#46; Eight subjects either with a history of prior positive PT to BAC &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#41;&#44; or a self-reported history of hand dermatitis after exposure to anti-bacterial skin products &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#41;&#44; and healthy controls &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#41; were enrolled&#46; Patch testing containing BACaq &#91;0&#46;15&#37; &#40;aqueous vehicle&#41;&#93;&#44; BACpet &#91;0&#46;15&#37; &#40;petrolatum vehicle&#41;&#93;&#44; BECaq &#40;0&#46;05&#37;&#41;&#44; BECpet &#40;0&#46;15&#37;&#41;&#44; BECaq &#40;0&#46;15&#37;&#41;&#44; BECaq &#40;0&#46;5&#37;&#41;&#44; SLSaq &#40;2&#37;&#41; positive irritant control&#44; and deionized water negative control were placed for 48<span class="elsevierStyleHsp" style=""></span>hours prior to removal&#46; Clinical grading and RCM imaging were performed on days 4 and 7 post-patch removal&#46; Similar to the findings in previous studies&#44; RCM features of ACD included SC disruption and parakeratosis&#44; microvesicle formation in the stratum granulosum&#44; stratum spinosum&#44; and dermo-epidermal junction&#46; Clinically positive reactions for BACaq 0&#46;15&#37; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#41; and BECaq 0&#46;15&#37; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#41; resulted in ACD characteristics that were noted on RCM analysis&#46; Positive clinical reactions for BECpet 0&#46;15&#37; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#41; were read as &#8216;subtle changes&#8217; on RCM&#59; clinically positive reactions from BECaq 0&#46;5&#37; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#41; were read as &#8220;possible&#8221; ACD&#46; There were no clinical reactions that resulted from exposure to BACpet 0&#46;15&#37; or BECaq 0&#46;05&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">24</span></a> Among the 10 patients who were exposed to SLSaq 2&#46;0&#37;&#44; 7 patients had positive clinical reactions&#44; with SC disruption&#44; parakeratosis&#44; and increased epidermal thickness on RCM analysis&#46; The data suggests that RCM can rectify that Quats are true allergens&#44; rather than irritants&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">24</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Another study by Astner <span class="elsevierStyleItalic">et al&#46;</span> compared clinical grading to combined technical evaluation methods &#91;RCM&#44; TEWL and fluorescent excitation spectroscopy &#40;FES&#41;&#93; in differentiating ACD and ICD<span class="elsevierStyleItalic">&#46;</span> Eighteen individuals with a history of ACD received two patches containing 4&#37; SLS&#44; a specific allergen&#44; a phosphate-buffered saline control&#44; and negative control&#46; Patches were removed 48<span class="elsevierStyleHsp" style=""></span>hours later&#44; and the participants returned at three or more time points &#40;2&#44; 3&#44; 4&#44; 9&#44; 14&#44; 21 days&#41; following patch removal&#46; At each visit&#44; clinical grading by two independent observers&#44; RCM evaluation&#44; and TEWL were performed&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">14</span></a> An FES excitation&#47;emission of 295&#47;345<span class="elsevierStyleHsp" style=""></span>nm corresponds to epidermal proliferation<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">25&#8211;28</span></a> and&#47;or increased cellular activity&#44;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">29</span></a> whereas an excitation band at 270<span class="elsevierStyleHsp" style=""></span>nm is consistent with inflammation&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">30</span></a> Significant stratum granulosum and stratum spinosum microvesicle formation&#44; but not SC changes&#44; peaked at 96-hours post-patch removal and persisted beyond the ninth day&#44; indicating ACD reactions are prolonged&#46; FES did not differ between ACD and control at either 278<span class="elsevierStyleHsp" style=""></span>nm or 298<span class="elsevierStyleHsp" style=""></span>nm&#44; thus FES alone cannot distinguish between ACD reaction or no reaction&#46; No significant correlation was observed between clinical scoring and TEWL measurements or RCM and TEWL&#44; but it is unclear if RCM corresponds to clinical scoring&#46; Despite insignificant correlation&#44; peak in TEWL&#44; a measure of SC disruption&#44; was delayed to the 4<span class="elsevierStyleSup">th</span> day post-patch removal&#46; This suggests that SC disruption occurs much later in ACD lesions when compared to ICD reactions&#46; It is possible that prior studies did not appreciate significant SC disruption in ACD lesions as readings were done within seven days&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">14</span></a> ICD reactions were detected by RCM within 48<span class="elsevierStyleHsp" style=""></span>hours of patch removal&#44; which is earlier than the identification of ACD reactions&#46; RCM features include SC disruption&#44; exocytosis&#44; spongiosis&#44; vesicle formation&#44; and epidermal necrosis&#46; In contrast to ACD&#44; ICD reaction sites had an increase in FES at 278<span class="elsevierStyleHsp" style=""></span>nm and 298<span class="elsevierStyleHsp" style=""></span>nm&#44; corresponding to increased inflammation&#44; epidermal proliferation&#44; and increased cellular activity&#44; which correlated with increased spongiosis&#44; parakeratosis&#44; and hyperkaratosis characteristics of irritant reactions&#46; It appears that FES can be used to detect presence of ICD reactions&#44; but not ACD&#46; Early reaction formation and resolution versus late reaction formation and resolution corresponds to ICD and ACD reactions by RCM&#44; respectively&#46; SC disruption&#44; as identified via RCM and increase in TEWL and FES&#44; is a key early structural change for irritant reactions that occur much later with allergen-exposure&#44; and helps to distinguish between the two dermatoses&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">14</span></a></p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">CONCLUSION</span><p id="par0090" class="elsevierStylePara elsevierViewall">RCM is emerging as a valid modality for diagnosing cutaneous malignancies and inflammatory dermatoses that&#44; in the past&#44; necessitated biopsy or patch testing&#46; RCM has a comparable sensitivity and specificity compared to patch testing for contact dermatitis &#40;92&#37; vs 85&#37; specificity and 82&#37; vs 85&#37; sensitive&#44; respectively&#41;&#46; When compared to histology&#44; RCM can identify SC disruption&#44; parakeratosis&#44; stratum spinosum spongiosis&#44; stratum granulosum spongiosis&#44; and exocytosis&#46; Multiple studies have shown RCM is effective at diagnosing ICD in both light- and dark-skinned patients&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Research has demonstrated that RCM can augment current PT diagnosis of CD&#46; RCM can detect sub-clinical ACD and ICD reactions&#46; It can help distinguish between doubtful-positive and negative ACD reactions&#46; RCM can detect pathological changes within minutes to a day when using patch testing&#46; This early reaction detection could change how PT is performed in the future&#46; RCM can be used to track dynamic changes in the skin&#44; such as treatment process and resolution&#46; It has been demonstrated that RCM can detect differences between ACD and ICD even when they appear morphologically similar&#44; helping distinguish these two entities&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Many of the RCM devices used in the studies herein were traditional RCM &#40;non-handheld&#41; devices&#46; These devices are limited by the imaging of curved skin surfaces on a live subject&#46; Lateral movement is controlled with the use of a tissue ring-and-window device attached to both the skin and device however&#44; breathing and minor movement create vertical motion artifact that may affect redundancy in stack image collection&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">31</span></a> Currently&#44; hand held confocal devices reduce technical limitations of traditional RCM devices&#46; Future generations of RCM devices can be improved to further address this technical limitation&#46; An additional limitation for RCM is the cost&#44; which is estimated to be 30&#44;000 USD&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">To date&#44; studies have identified RCM features that can detect subclinical reactions to differentiate morphologically similar lesions &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; Further studies should aim to examine the difference in ACD presentation in different Fitzpatrick types&#44; much like what has been done for ICD&#46; Studies are also needed to optimize RCM image protocol and laser settings that are most suitable for each condition&#44; anatomical location&#44; and Fitzpatrick skin type&#46; Pilot studies are needed to identify RCM features in other inflammatory dermatoses in order to compare features among various erythematosquamous conditions&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span></span>"
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          "titulo" => "MATERIALS AND METHODS"
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          "titulo" => "REVIEW OF LITERATURE"
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              "titulo" => "Allergic Contact Dermatitis"
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              "titulo" => "Irritant Contact Dermatitis"
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              "identificador" => "sec0035"
              "titulo" => "Comparing Allergic Contact Dermatitis and Irritant Contact Dermatitis"
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          "titulo" => "CONCLUSION"
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            0 => "Reflectance confocal microscopy"
            1 => "In vivo microscopy"
            2 => "Allergic contact dermatitis"
            3 => "Irritant contact dermatitis"
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            0 => "Microscopia confocal de reflectancia"
            1 => "Microscopia in vivo"
            2 => "Dermatitis al&#233;rgica de contacto"
            3 => "Dermatitis irritativa de contacto"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Dermatologic diagnosis and monitoring have been dependent largely on visual grading&#46; A skin biopsy is performed in case of diagnostic uncertainty&#44; but can be traumatic&#44; and results are delayed due to time for specimen transport and processing&#46; Biopsies also destroy specimens&#44; prohibiting lesion evolution monitoring&#46; In vivo reflectance confocal microscopy &#40;RCM&#41; offers a diagnostic alternative to skin biopsy&#46; RCM captures real-time&#44; high-resolution images&#44; and has been piloted for the evaluation of various dermatologic conditions&#46; Identification of unique RCM features may distinguish dermatoses with similar clinical morphologies&#46; Allergic contact dermatitis &#40;ACD&#41; and irritant contact dermatitis &#40;ICD&#41; are diagnosed by patch testing that currently uses a subjective scoring system&#46; RCM has increasingly been studied for early detection and severity grading of CD&#46; Common RCM features shared by ACD and ICD are stratum corneum disruption&#44; vesicle formation&#44; exocytosis&#44; spongiosis&#44; and parakeratosis&#46; Features unique to ACD are vasodilation&#44; increased epidermal thickness&#44; intercellular edema&#44; and acanthosis&#46; Features unique to ICD are detached corneocytes and targetoid keratinocytes&#46; This review summarizes the use of RCM in evaluating contact eccematous conditions and aims to spark future research and interest in this promising tool&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Tanto el diagn&#243;stico como el seguimiento en la dermatolog&#237;a depender&#225;n en gran medida de una evaluaci&#243;n visual&#46; Cuando no se puede llegar al diagn&#243;stico&#44; se procede a realizar una biopsia cut&#225;nea&#44; un procedimiento invasivo y que con frecuencia los resultados retrasan debido a la demora del transporte&#44; as&#237; como al procesamiento de la muestra&#46; Por otro lado&#44; las biopsias pueden destruir las lesiones&#44; lo que imposibilitar&#225; realizar un seguimiento cl&#237;nico de la evoluci&#243;n de la lesi&#243;n a estudio&#46; La microscopia confocal de reflectancia in vivo &#40;MCR&#41; ofrece una alternativa diagn&#243;stica a la biopsia cut&#225;nea&#46; Esta t&#233;cnica captura en tiempo real im&#225;genes de alta resoluci&#243;n y se utilizar&#225; en la evaluaci&#243;n de diversas condiciones dermatol&#243;gicas&#46; La identificaci&#243;n de caracter&#237;sticas espec&#237;ficas en la MCR podr&#237;a ayudar a diferenciar dermatosis con una morfolog&#237;a cl&#237;nica similar&#46; La dermatitis al&#233;rgica de contacto &#40;DAC&#41; y la dermatitis irritativa de contacto &#40;DIC&#41; se diagnostican generalmente gracias a pruebas epicut&#225;neas&#59; estas&#44; a su vez&#44; se basar&#225;n en un sistema de valoraci&#243;n subjetiva&#46; El uso de la MCR tanto en la detecci&#243;n temprana&#44; como en la clasificaci&#243;n de la intensidad de la DC&#44; ha sido estudiado en m&#250;ltiples estudios&#46; Existir&#225;n algunas caracter&#237;sticas comunes en la MCR de la DAC como de la DIC&#46; Entre estas podemos se&#241;alar la disrupci&#243;n del estrato c&#243;rneo&#44; la formaci&#243;n de ves&#237;culas&#44; la exocitosis&#44; la espongiosis y la paraqueratosis&#46; Las caracter&#237;sticas espec&#237;ficas para la DAC ser&#225;n la presencia de vasodilataci&#243;n&#44; el aumento del grosor epid&#233;rmico&#44; edema intercelular y acantosis&#46; Las caracter&#237;sticas espec&#237;ficas de la DIC son la presencia de los corneocitos disgregados y queratinocitos en diana&#46; Esta revisi&#243;n resume la utilidad de la MCR en las condiciones eccematosas de contacto cut&#225;neas y busca incentivar futuras investigaciones&#44; as&#237; como incrementar el inter&#233;s cl&#237;nico en esta prometedora t&#233;cnica&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58;&#46;</p>"
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      1 => array:1 [
        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">&#46; Microscopia confocal de reflectancia in vivo&#58; papel emergente en el diagn&#243;stico no invasivo&#44; as&#237; como en el seguimiento de las dermatosis eccematosas Actas Dermosifiliogr&#46; 2019&#59;110&#58;626&#8211;636&#46;</p>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A A low power &#40;&#60;30 mW&#41;&#44; tissue-sparing laser includes a laser light source&#44; scanning elements&#44; relay telescope&#44; beam splitter&#44; pinhole aperture&#44; objective lens&#44; and detector to generate images of dark and bright cutaneous structures&#46;</p> <p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Figure 1B&#58; Representative stacking of imaging&#44; revealing characteristics from the epidermis to the upper reticular dermis&#46;</p>"
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">A Allergic Contact Dermatitis&#58; Reflectance confocal microscopy image &#40;0&#46;5<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>0&#46;5<span class="elsevierStyleHsp" style=""></span>mm&#41; at the level of the spinous layer &#40;&#8764;30 microns depth&#41; shows spongiosis and exocytosis &#40;yellow arrow&#41; and multiple microvesicles with lymphocytes and detached keratinocytes &#40;red arrow&#41;&#46;</p> <p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Figure 2B&#58; Irritant contact dermatitis&#58; Reflectance confocal microscopy image &#40;0&#46;5<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>0&#46;5<span class="elsevierStyleHsp" style=""></span>mm&#41; shows disruption of stratum corneum with detached corneocytes and early parakeratosis &#40;yellow arrows&#41; and confluence of microvesicles with inflammatory cells infiltration &#40;red arrow&#41; below&#46;</p>"
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Faint erythema only&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Doubtful rxn&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Erythema&#44; infiltration&#44; possibly papules&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Weak positive rxn&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Erythema&#44; infiltration&#44; papules&#44; vesicles&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Strong positive rxn&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Intense erythema&#44; infiltrate&#44; coalescing vesicles&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Extreme positive rxn&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Various morphologies&#44; eg&#46; bulla&#44; necrosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Irritant rxn&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2142227.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">International Contact Dermatitis Research Group Scoring System&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; RCM&#58; Reflectance Confocal Microscopy&#59; CD&#58; Contact Dermatitis&#59; ACD&#58; Allergic Contact Dermatitis&#59; SC&#58; Stratum Corneum&#59; SS&#58; Stratum Spinosum&#59; SG&#58; Stratum Granulosum&#59; ICD&#58; Irritant Contact Dermatitis&#59; SLS&#58; Sodium Lauryl Sulfate</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Reference&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Condition&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patient &#40;N&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Allergens&#47; Irritants Used&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">RCM Features&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Koller <span class="elsevierStyleItalic">et al&#46;</span><a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">17</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Unspecified CD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20 CD lesions and 10 healthy controls&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Not mentioned&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RCM detected CD with 83&#37; sensitivity and 92&#37; specificityExocytosisEpidermal edemaDermal vasodilatationIntraepidermal vesicle formation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Gonzalez <span class="elsevierStyleItalic">et al&#46;</span><a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">18</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ACD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nickel sulfate 5&#37;&#44; Balsam of Peru 25&#37;&#44; and Fragrance mix 8&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Immediate patch removal&#58;VesiclesExocytosis of lymphocytes and Langerhans cells24<span class="elsevierStyleHsp" style=""></span>hours post patch removal&#58;Dendritic cellsParakeratosis48 and 72<span class="elsevierStyleHsp" style=""></span>hours post patch removal&#58;SC disruptionSpongiosisIncreased volume and diameter of dermal vasculature&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Astner <span class="elsevierStyleItalic">et al&#46;</span><a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">7</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ACD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8220;Specific allergen&#8221;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SC disruptionParakeratosisSS spongiosis &#40;sensitivity 100&#37;&#44; specificity 93&#37;&#41;SG spongiosis &#40;sensitivity 96&#37;&#44; specificity 96&#37;&#41;Exocytosis &#40;sensitivity 100&#37;&#44; specificity 74&#37;&#41;SS and SG vesicle formationSS and SG inflammatory infiltrate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Samhaber <span class="elsevierStyleItalic">et al&#46;</span><a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">19</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ACD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8220;Relevant allergen&#8221;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Epidermal spongiosisIncreased vascularizationSS and SG inflammatory infiltrateSS and SG microvesicles&#47;vesiclesParakeratosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sakanashi <span class="elsevierStyleItalic">et al&#46;</span><a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">20</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ACD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11 volunteers with contact allergy and 8 healthy volunteers&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#37; nickel sulfate and 2&#37; cobalt chloride&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Increased suprabasal epidermal thicknessIntercellular edemaAcanthosisGreat vesicle formation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Astner <span class="elsevierStyleItalic">et al&#46;</span><a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">21</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ICD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 Caucasians and 10 healthy AA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Caucasians&#58; 10&#37; &#40;threshold&#41; and 5&#37; &#40;subthreshold&#41; irritant solutionAA&#58; 25&#37; &#40;threshold&#41; and 20&#37; &#40;subthreahold&#41; irritant solution&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SC disruptionParakeratosisCorneocytesSpongiosisSS and SG vesicle formation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hicks <span class="elsevierStyleItalic">et al&#46;</span><a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">22</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ICD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 Caucasians and 6 healthy AA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#37; SLS&#44; 4&#37; SLS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SpongiosisVesicle formationSC disruptionFocal parakeratosisExocytosisMicrovesicles containing inflammatory cells and detached keratinocytesPerivascular inflammatory infiltrate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Casari <span class="elsevierStyleItalic">et al&#46;</span><a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">23</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ICD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#37; SLS &#40;Observed difference in RCM features following Vitamin E product application&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Compared to control&#44; Vitamin E reduced the concentration of&#58;Detached corneocytesTargetoid and bright keratinocytes &#40;necrotic&#47;apoptotic cells&#41;Irregular keratinocyte architecture in the SS and SGIrregular rings in the DEJ&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Benjamin <span class="elsevierStyleItalic">et al&#46;</span><a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">24</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ACD and ICD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;15&#37; BACaq&#44; 0&#46;15&#37; BACpet&#44; 0&#46;05&#37; BECaq&#44; 0&#46;15&#37; BECpet&#44; 0&#46;15&#37; BECaq&#44; 0&#46;5&#37; BECaq&#44; 2&#37; SLSaq&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ACDSC disruption and parakeratosisMicrovesicle formation in the SS&#44; SG&#44; and DEJICDSC disruption and parakeratosisIncreased epidermal thickness&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Astner <span class="elsevierStyleItalic">et al&#46;</span><a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">32</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ACD and ICD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#37; SLS and a specific allergen&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ACD &#91;Delayed and prolonged &#40;96<span class="elsevierStyleHsp" style=""></span>hours post-patch removal&#41;&#93;SG and SS microvesicle formationICD &#91;Early &#40;within 48<span class="elsevierStyleHsp" style=""></span>hours post-patch removal&#41;&#93;SC disruptionExocytosisSpongiosisVesicle formationEpidermal necrosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
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        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ACD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ICD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Disruption of SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Spongiosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X &#40;particularly of SS&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Parakeratosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vesicle formation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X &#40;microvesicles&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Exocytosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Inflammatory cell infiltrate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vasodilation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Epidermal thickness&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Intercellular edema&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Acanthosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Detached corneocytes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Targetoid keratinocytes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                      "titulo" => "Memoir on inventing the confocal scanning microscope"
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                      "titulo" => "In vivo confocal scanning laser microscopy of human skin&#58; Melanin provides strong contrast"
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                            0 => "M&#46; Rajadhyaksha"
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                      "doi" => "10.1111/1523-1747.ep12606215"
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                        "tituloSerie" => "J Invest Dermatol&#46;"
                        "fecha" => "1995"
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                        "paginaInicial" => "946"
                        "paginaFinal" => "952"
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