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and beta &#40;HCoV-JHKU1&#44; HCoV-OC43&#41; had been identified as endemic in humans&#46; In 2002&#44; there was an outbreak in China of a coronavirus that caused severe acute respiratory syndrome &#40;SARS&#41;&#46; The virus was named SARS-CoV&#44; and mortality was reported at around 10&#37;&#46; In 2012&#44; a respiratory syndrome caused by a coronavirus from the Middle East &#40;MERS-CoV&#41; was identified in Saudi Arabia&#46; In this case&#44; the mortality was 35&#37;&#46; SARS-CoV-2 is the new member of this group&#46; Disease associated with the virus is denoted coronavirus disease-19 &#40;COVID-19&#41;&#44; thus avoiding any geographical qualification&#46; The virus propagated out of control and the outbreak was declared a pandemic by the World Health Organization &#40;WHO&#41; in March 2020&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The most frequent manifestations of infection with SARS-CoV-2 include fever&#44; dry cough&#44; and dyspnea&#59; less frequent are odynophagia&#44; gastrointestinal symptoms&#44; and anosmia or ageusia&#46; A high proportion of patients develop pneumonia&#44; often bilaterally&#44; and this may lead to respiratory failure and the need for respiratory support in more than 6&#37; of cases&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Around 30&#37; will require admission to hospital&#44; and 5&#37; to 10&#37; will need admission to intensive care units &#40;ICUs&#41;&#46; Mortality varies widely&#44; from around 2&#37; to somewhat greater than 10&#37; in some countries&#44;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> and it appears higher in older individuals and those with comorbidities and marked respiratory compromise&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Infection can also occur without symptoms or with very mild symptoms&#44; and patients with these forms are probably potent vectors helping to spread infection&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Pathogenesis</span><p id="par0025" class="elsevierStylePara elsevierViewall">From the pathogenic point of view&#44; the immune response triggered by infection with SARS-CoV-2 may result in harmful effects&#44; such as endothelial cell dysfunction and activation of coagulation pathways&#59; this may explain the cardiovascular and thrombotic complications that affect a subgroup of patients&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The <span class="elsevierStyleItalic">corona</span> &#40;or crown&#41; of this virus is formed from protruding glycoproteins that form spikes&#46; These structures are what enables the virus to establish itself in the host&#46; The infection process occurs by binding to receptors of angiotensin converting enzyme 2 &#40;ACE2&#41;&#44; a membrane protein expressed in the cardiovascular system&#44; kidneys&#44; gastrointestinal system&#44; and lungs&#46; This enzyme is implicated in activation of the renin-angiotensin-aldosterone system &#40;RAAS&#41;&#46; ACE2&#44; 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In normal conditions&#44; these are components of immune protection&#46; However&#44; in some patients&#44; the immune response is pathogenic or dysregulated&#44; with exaggerated release of IL-1&#946;&#44; IL-6&#44; and IFN-&#947;&#59; epithelial cell apoptosis&#59; and increased vascular permeability&#46; These events may lead to the development of SARS&#44; in which obliteration of the alveoli&#44; formation of typical hyaline membranes&#44; and hyperplasia of type II pneumocytes have been observed&#46; The terms coined for this exaggerated inflammation are <span class="elsevierStyleItalic">cytokine storm</span> or <span class="elsevierStyleItalic">cytokine release syndrome</span>&#46; Blood workup often shows lymphopenia&#44; with elevated values for inflammatory indicators &#40;C-reactive protein&#44; ferritin&#44; <span class="elsevierStyleSmallCaps">d</span>-dimer&#44; IL-6&#44; and procalcitonin&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">In addition&#44; the pattern of tissue damage observed in lung samples and some skin samples taken from patients with severe COVID-19 suggest occlusive microvascular damage mediated by complement activation of both the alternative pathway and the lectin-associated pathway&#46; Capillary damage has been found with extensive deposition of the C5b-9 membrane attack complex&#44; C4d&#44; and mannose-binding lectin-associated serine protease 2 &#40;MASP2&#41; in the lungs&#46; There have also been reports of a pattern of microvascular thrombotic disease mediated by complement in the skin of patients similar to that seen in livedo racemosa lesions and retiform purpura&#44; with C5b-9 and C4d deposition&#46; Activation of these mechanisms and interference in ACE2 function in target tissues due to viral action leads to an increase in angiotensin II&#44; associated with greater inflammation and oxidative stress&#46; The release of these reactive oxygen species and interference in antioxidant activity may increase complement activiation&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Skin Manifestations</span><p id="par0040" class="elsevierStylePara elsevierViewall">Articles published at the start of the pandemic in China considered skin manifestations as a minor and nonspecific sign&#44; with rash reported in 0&#46;2&#37; of patients&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> However&#44; this observation may presumably have been conditioned by the lack of dermatologists caring for patients affected by COVID-19 at the start of the outbreak&#46; Recalcati&#44;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> who was a dermatologist&#44; observed skin manifestations in 20&#46;4&#37; of a group of 88 patients with COVID-19&#59; in some cases&#44; these manifestations were present from the start whereas others appeared during or after admission to hospital&#46; Hedou et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> in response to the aforementioned article&#44; reported skin lesions attributable to COVID-19 in 4&#46;9&#37; of patients with a positive polymerase chain reaction &#40;PCR&#41; test result in a series of 103 patients&#46; However&#44; the real incidence of skin manifestations in infection by SARS-CoV-2 is not known&#44; bearing in mind that at the time&#44; the focus was on patients with severe signs or symptoms&#44; and diagnosis was made in many patients with no or limited symptoms following a telephone call by the patient to the primary care physician&#44; without any face-to-face visits&#44; and therefore no skin examination &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">Fern&#225;ndez-Nieto et al&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> reported difficulties facing dermatologists for taking samples and even clinical images in a pandemic that requires rigorous isolation measures&#44; and this is a barrier to conducting reliable epidemiological studies&#46; For these procedures&#44; transparent bags can be considered both for transporting photographic equipment and the tools necessary for taking biopsies&#46; The COVID-19 pandemic represents a completely new scenario for dermatologists&#44; and this situation may be prolonged&#44; depending on how the pandemic progresses&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The recent article by Galv&#225;n et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> supported by the Spanish Academy of Dermatology and Venereology &#40;AEDV&#41;&#44; reported heterogeneous and complex skin manifestations associated with COVID-19 infection&#46; The authors studied a group of 375 patients prospectively enrolled in several Spanish hospitals for 2 weeks during the peak of the pandemic&#46; They identified 5 main clinical patterns related to COVID-19&#58; acral areas of erythema with vesicles or pustules &#40;pseudochilblain pattern&#41; &#40;19&#37;&#41;&#44; vesicular rashes &#40;9&#37;&#41;&#44; urticarial lesions &#40;19&#37;&#41;&#44; maculopapular lesions &#40;47&#37;&#41;&#44; and livedo or necrosis &#40;6&#37;&#41;&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The following paragraphs describe the most important clinical features and diagnostic and prognostic implications in patients with SARS-CoV-2 infection&#46;</p><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Acral or Acroischemic Lesions</span><p id="par0060" class="elsevierStylePara elsevierViewall">The acral pseudochilblain pattern of lesions&#44; reported by Galv&#225;n et al&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> as acral&#44; erythematous&#44; and edematous lesions&#44; with formation of vesicles and pustules&#44; are perhaps the most characteristic skin lesions associated with the SARS-CoV-2 pandemic&#46; The description and reporting of these lesions initially occurred outside academic circles in an informal fashion in medical or dermatological social media&#44; based on shared images from family members&#44; acquaintances&#44; and colleagues&#46; The first case published reported an adolescent aged 13 years who developed purpuric lesions on the feet prior to developing systemic symptoms such as fever&#44; muscle pain&#44; and headache&#44; in a family with suspected cases of COVID-19 infection at the time the pandemic in Italy was spreading rapidly&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> However&#44; no specific microbiological studies were performed&#46; In the article&#44; the authors mentioned the existence of an epidemic of similar lesions in children with suspected COVID-19 in Italy&#46; In the series by Galv&#225;n et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> the pattern of pseudochilblain lesions was the second most common skin manifestation &#40;19&#37;&#41;&#46; They developed in young patients&#44; generally late on in the course of the disease&#44; and were present for a period of 12&#46;7 days&#44; in general&#44; in patients with mild disease or asymptomatic individuals&#46; These lesions were described as painful &#40;32&#37;&#41; or itchy &#40;30&#37;&#41;&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">From the clinical point of view&#44; the pseudochilblain pattern of lesions consists of macules&#44; papules&#44; or plaques&#44; often about a millimeter in size&#44; and usually with a clearly defined border in the metatarsophalangeal area&#44; although the whole of the finger or toe can be involved &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Often&#44; only some fingers or toes are affected while others completely lack any involvement&#44; and at times&#44; these lesions may be accompanied by lesions in the palmar and plantar region&#46; They usually affect the feet and&#44; to a lesser degree&#44; the hands&#46; Initially purpuric or bluish&#44; they can form blisters or scabs during the course of the disease&#59; at times&#44; they may resemble multiform erythema<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> or vasculitis&#59; in fact&#44; some authors recognize a multiform erythema type subgroup&#44;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#8211;15</span></a> with targetoid or atypical target lesions&#44; which can be associated with lesions in extensor areas&#44; such as the elbows&#46; In cases with histological study&#44; a lymphocytic infiltrate is reported in the superficial and deep dermis&#44; of perivascular predominance&#44; occasionally associated with edema and signs of endothelial activation&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Keratinocyte necrosis and perieccrine reinforcement may be present&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">Alramthan and Aldaraji&#44;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> reporting 2 clinical cases in young adults&#44; proposed the hypothesis&#44; not confirmed with histology in their own cases&#44; that formation of hyaline thrombi in small caliber vessels of different organs observed in autopsies of patients could explain the pseudochilblain characteristics of the lesions&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Fewer than half the cases had microbiological or serological test results available &#40;specific PCR or rapid antibody test for IgM&#47;IgG&#41;&#46; In general&#44; when assessed&#44; laboratory abnormalities or elevations have generally been lacking in measures of inflammation such as D-dimer&#44; C reactive protein &#40;CRP&#41;&#44; or lactate dehydrogenase &#40;LDH&#41;&#44; indicative of poor prognosis for this disease&#46; The strongest evidence of association with viral infection was therefore that presentation occurred during the pandemic &#40;and in a different context to that of chilblains&#44; in the warmer months than when they usually appear&#41; and a history in the family environment or personal situation consistent with infection&#46; The authors suggested these negative results were due to the late development of these lesions in the course of the disease&#59; the low sensitivity of the tests used&#44; which has led to mass recall of some batches&#59; and the rapid disappearance of antibodies&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;15</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Docampo-Sim&#243;n et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> in the first prospective study of skin manifestations&#44; found a positive PCR result in only 1 of the 38 samples tested&#46; In addition&#44; due to the aforementioned technical reasons &#40;time since infection&#44; false negatives&#41;&#44; the authors considered the possibility that this manifestation simply has nothing to do with COVID-19&#46; Other possible explanations could be a traumatic origin during lock-down or even the concurrent expansion of another virus&#44; such as parvovirus B19&#46; This possible relation with the lock-down period&#44; and not necessarily with COVID-19&#44; has also been suggested in a recent series with similar results&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">During the worst weeks of the pandemic&#44; we saw patients with these characteristics almost on a daily basis in our clinics&#46; From both the clinical and epidemiological point of view&#44; the characteristics are consistent with those described above&#46; Most of our patients were young&#44; asymptomatic or with mild symptoms&#44; and not one of them had a serious complication associated with COVID-19&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Vesicular and Chickenpox-Like Lesions</span><p id="par0090" class="elsevierStylePara elsevierViewall">In 8 Italian centers&#44; clinical data were collected from patients with COVID-19&#44; with microbiological confirmation by RT-PCR from a nasopharyngeal swab and with no history of medications that could have triggered chickenpox-like lesions&#46; In total&#44; the study included 22 patients&#44; mainly males&#44; with a mean age of 60 years&#46; The lag from the onset of symptoms of COVID-19 to development of skin manifestations was relatively short&#44; 3 days &#40;range&#44; 2 to 12 days&#41;&#46; Most patients presented with the full clinical manifestations of the disease&#44; with general and respiratory manifestations&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">Vesicular lesions&#44; usually monomorphic&#44; appear early on and may at times precede other symptoms &#40;in 15&#37; of patients&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> although in most cases&#44; up to 79&#46;2&#37; in a series of 24 patents reported by Fernandez-Nieto et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> they occur at the onset of other symptoms&#46; There is involvement of the trunk in almost all cases and in 20&#37; the limbs are also affected &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; Exceptionally&#44; facial and mucosal involvement have been reported&#46; The skin lesions are barely symptomatic&#44; but when they do cause symptoms&#44; these are usually mild itching and&#44; to a lesser extent pain or burning sensation&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;19</span></a> Although the lesions may be disperse&#44; an extensive disseminated pattern is more frequent&#44; 75&#37; according to Fernandez-Nieto et al&#46; In some patients&#44; the legs may be affected&#44; or the lesions may present with hemorrhagic content or be large&#44; with a diffuse distribution&#46; The mean duration of skin symptoms is 10&#46;4 days &#40;&#177;9&#46;3&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> In cases in which a biopsy was obtained&#44; the findings were described as consistent with viral infection&#44; showing vacuolar abnormalities and abnormal maturation of keratinocytes&#44; as well as larger&#44; multinucleated keratinocytes&#44; and dyskeratosis&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> There have been no reports of presence of SARS-Cov-2 confirmed with positive PCR in biopsies of skin lesions&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Urticarial Rash</span><p id="par0100" class="elsevierStylePara elsevierViewall">Henry et al&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> reported the case of a female patient who developed an urticarial rash&#44; accompanied by odynophagia and arthralgia&#44; before developing the full clinical manifestations of COVID-19&#46; Van Damme et al&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> reported a further 2 cases of urticarial rash as the first clinical manifestation of COVID-19&#44; although microbiological confirmation of infection was only obtained in 1 of those&#44; and in both cases the skin manifestations preceded pyrexia&#46; One of the patients developed severe respiratory failure&#44; leading to death&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Urticarial rash accounts for 19&#37; of skin manifestations in COVID-19&#46; In general&#44; these skin manifestations become evident more or less at the same time as other general and respiratory symptoms&#46; Lesions occur predominantly on the trunk&#44; and involvement of the face and hands is frequent&#44; with resolution in approximately 7 days&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> In one of the cases reported&#44; histological study showed edema of the upper dermis and perivascular lymphocytic infiltration&#44; with some eosinophils present&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Although such lesions may be associated with worse prognosis in some patients&#44;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> this is a nonspecific rash&#44; and it has been reported in patients with a favorable clinical outcome and those with limited symptoms&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">There is probably a certain degree of variability in the way in which rashes are reported as urticarial maculopapular because&#44; in the cases described&#44; it is not specified whether the lesions follow a transient course or not&#46; These are nonspecific rashes in which it is difficult to establish a solid relationship with viral infection&#44; bearing in mind that the patients who present with these lesions have often received a range of treatments such as antiviral agents&#44; antibiotics&#44; hydroxychloroquine&#44; anticoagulants&#44; and support treatments&#44; and these could also trigger skin reactions &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; In fact&#44; in a histological study&#44; some cases of vacuolar interface dermatitis were observed with occasional necrotic keratinocytes&#44; findings more reminiscent of a multiform erythematous pattern&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Maculopapular Rash</span><p id="par0115" class="elsevierStylePara elsevierViewall">This group of lesions includes a heterogeneous group of rashes that&#44; considered together&#44; and given the difficulty of further subclassification&#44; account for 47&#37; of the skin manifestations in patients with COVID-19&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> At times&#44; these rashes may be accompanied by a petechial component or with macules or more extensive areas with a purpuric appearance&#46; In other cases&#44; the lesions have a markedly perifollicular distribution &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41; with variable degrees of scaling&#44; some of which have been reported as similar to pityriasis rosea&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> Infiltrated papules have also been observed&#59; these are pseudovesicular lesions or similar to erythema elevatum diutinum or multiform erythema&#44; and they may occasionally be pruritic &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> A markedly craniocaudal development has also been reported&#44; with involvement of the folds but without the palmoplantar region or the mucosa being affected&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">27&#44;28</span></a></p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><elsevierMultimedia ident="fig0025"></elsevierMultimedia><p id="par0120" class="elsevierStylePara elsevierViewall">Jimenez-Cauhe et al&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> reported the case of a female patient who developed a coalescent erythematous-purpuric rash about a millimeter in size&#44; with a flexural distribution predominantly in the periaxillary region&#46; The authors considered the difficulty of associating the skin manifestations with viral infection in view of its nonspecific appearance and concomitant medication use&#46; Other authors have reported the appearance of rash that resembles the typical skin involvement of symmetrical drug-related intertriginous and flexural exanthema &#40;SDRIFE&#41;&#44; possibly associated with viral infection&#44; given that the rash resolved despite continued use of the drug&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> We have also observed a similar distribution in our own patients &#40;<a class="elsevierStyleCrossRef" href="#fig0030">Fig&#46; 6</a>&#41;&#46; From the histological point of view&#44; a range of features have been reported within the group of maculopapular rashes&#44; such as a perivascular inflammatory infiltrate with discrete lymphocytic exocytosis&#44; marked vessel dilatation in the superficial and medial dermis&#44; as well as lymphocytic vasculitis&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">31&#44;32</span></a></p><elsevierMultimedia ident="fig0030"></elsevierMultimedia><p id="par0125" class="elsevierStylePara elsevierViewall">There is limited additional information in these patients regarding the timing with respect to other clinical manifestations or its prognostic or diagnostic value&#46; In most cases&#44; maculopapular rashes appear either at the same time as the characteristic respiratory symptoms or a few days later&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;28&#44;32&#44;33</span></a> However&#44; in our hospital&#44; we have detected more or less generalized maculopapular rashes&#44; in some cases similar to multiform erythema&#44; in young patients with a history of mild or even no symptoms&#44; although with epidemiological evidence of infection with SARS-CoV-2 and these resemble those that can be seen in other viral infections&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Livedoid or Necrotic Lesions</span><p id="par0130" class="elsevierStylePara elsevierViewall">Livedoid or necrotic lesions are relatively uncommon&#44; accounting for 6&#37; of skin lesions in the series reported by Galv&#225;n et al&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> These are lesions usually reported in elderly patients with prior comorbidities and with severe forms of COVID-19 infection&#46; They are considered secondary to vascular micro-occlusion and acral ischemia due to general deterioration in the patient&#39;s state and&#47;or the coagulation disorders attributed to COVID-19<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;5</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0035">Fig&#46; 7</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> However&#44; in some patients&#44; episodes have been reported of patchy livedo reticularis that presented over the course of minutes or hours&#44; of an uncertain nature and a benign course&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a></p><elsevierMultimedia ident="fig0035"></elsevierMultimedia><p id="par0135" class="elsevierStylePara elsevierViewall">In the histological study of cutaneous purpuric lesions&#44; a pauci-inflammatory thrombogenic vasculopathy has been found&#44; with C5b-9 and C4d deposits&#44; and localization of viral particles&#44; leading to suspicion of the presence of a catastrophic microvascular lesion caused by complement activation&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conclusions</span><p id="par0140" class="elsevierStylePara elsevierViewall">The SARS-CoV-2 pandemic has had a major impact from the healthcare&#44; economic&#44; and societal point of view&#44; and will probably lead to lasting changes in our generation&#46; Considered initially as of little relevance&#44; the dermatological manifestations have proved to be varied and complex&#46; Recent efforts to characterize cutaneous involvement in patients with COVID-19&#44; implemented in a study conducted quickly and rigorously in a full health emergency&#44; has identified 5 main groups of lesion &#40;acral&#44; vesicular&#44; urticarial&#44; maculopapular and livedoid&#47;necrotic lesions&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> Although these manifestations are considered a reflection of different pathogenic pathways&#44; with a variable implication of the viral infection&#44; inflammatory processes&#44; and vascular and systemic complications of the disease&#44; there is a substantial knowledge gap in many aspects&#46; Thus&#44; it cannot be ruled out that acral lesions&#44; reported as characteristic given the epidemiological evidence rather than microbiological tests in most cases&#44; may not be directly related to COVID-19&#46; Extensive urticarial or maculopapular rashes&#44; often described in symptomatic or even hospitalized patients&#44; may be linked in many cases to drugs able to trigger them&#44; such as hydroxychloroquine or antibiotics&#44; administered during the COVID-19 pandemic despite limited evidence of their effectiveness&#46; Finally&#44; the heterogeneous set of maculopapular rashes consistent with viral infection&#44; multiform erythema&#44; or SDRIFE&#44; may be associated with other etiologic agents neglected during the pandemic&#44; as in many cases&#44; microbiological or serologic confirmation of SARS-CoV-2 infection is lacking&#46; Thus&#44; in the panorama of lesions associated with COVID-19&#44; for the most part&#44; priority in the international literature during the peak of the pandemic was given to rapid publication&#44; even though the description&#44; support&#44; or methodological rigor were not ideal&#46; Familiarity with the skin manifestations may allow not only greater investigation into aspects still little known in COVID-19&#44; but also may help a more rapid diagnosis and even serve as a prognostic marker&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Conflicts of Interest</span><p id="par0145" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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            0 => "COVID-19"
            1 => "SARS-CoV-2"
            2 => "Piel"
            3 => "Acral"
            4 => "Ves&#237;culas"
            5 => "Urticaria"
            6 => "Exantema"
            7 => "Livedo"
            8 => "Virosis"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">The coronavirus 2019 &#40;COVID-19&#41; pandemic&#44; caused by severe acute respiratory syndrome coronavirus 2 &#40;SARS-CoV-2&#41;&#44; has had enormous health&#44; economic&#44; and social consequences&#46; The clinical spectrum of cutaneous manifestations observed in patients with COVID-19 is both heterogeneous and complex&#46; To date&#44; reports have identified 5 main categories&#58; acral lesions&#44; vesicular rashes&#44; urticarial rashes&#44; maculopapular rashes&#44; and livedoid and necrotic lesions&#46; However&#44; these will probably be modified as new information comes to light&#46; Cutaneous manifestations associated with COVID-19 probably reflect the activation of pathogenic pathways by the virus or a response to inflammatory processes&#44; vascular or systemic complications&#44; or even treatments&#46; Familiarity with the cutaneous manifestations of COVID-19 may enable early diagnosis or help guide prognosis&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">La pandemia por SARS-CoV-2 ha causado un gran impacto desde el punto de vista sanitario&#44; econ&#243;mico y social&#46; La semiolog&#237;a dermatol&#243;gica se ha demostrado heterog&#233;nea y compleja&#46; En la actualidad se han definido cinco grupos principales de manifestaciones cut&#225;neas asociadas a la COVID-19&#58; lesiones acrales&#44; exantemas vesiculares&#44; erupciones urticariales&#44; exantemas maculopapulares y lesiones livedoides&#47;necr&#243;ticas&#46; Sin embargo&#44; es probable que esta clasificaci&#243;n se modifique en el futuro&#46; La cl&#237;nica cut&#225;nea es probablemente el reflejo de distintas v&#237;as patog&#233;nicas con implicaci&#243;n variable de la infecci&#243;n v&#237;rica&#44; del proceso inflamatorio&#44; de las complicaciones vasculares o sist&#233;micas de la enfermedad o incluso de los tratamientos administrados&#46; El conocimiento de las manifestaciones cut&#225;neas puede permitir un diagn&#243;stico precoz o incluso servir como marcador pron&#243;stico&#46;</p></span>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Carrascosa JM&#44; Morillas V&#44; Bielsa I&#44; Munera-Campos M&#46; Manifestaciones cut&#225;neas en el contexto de la infecci&#243;n por SARS-CoV-2 &#40;COVID-19&#41;&#46; Actas Dermosifiliogr&#46; 2020&#46; <span class="elsevierStyleInterRef" id="intr0005" href="https://doi.org/10.1016/j.ad.2020.08.002">https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1016&#47;j&#46;ad&#46;2020&#46;08&#46;002</span></p>"
      ]
    ]
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Acral pseudochilblain papule&#46;</p>"
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      1 => array:8 [
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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Disperse monomorphic papulovesicles on the trunk&#46;</p>"
        ]
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      2 => array:8 [
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Maculopapular rash in a patient with COVID-19 associated with bilateral pneumonia&#44; who received different drugs&#46; Differential diagnosis with respect to toxicoderma is difficult&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "fig0020"
        "etiqueta" => "Figure 4"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
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            "identificador" => "at0020"
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Nonspecific rash&#44; with perifollicular distribution in a patient with COVID-19&#46;</p>"
        ]
      ]
      4 => array:8 [
        "identificador" => "fig0025"
        "etiqueta" => "Figure 5"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Multiform erythema-like eruption in a patient with SARS-CoV-2 infection&#46;</p>"
        ]
      ]
      5 => array:8 [
        "identificador" => "fig0030"
        "etiqueta" => "Figure 6"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
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        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0030"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Periaxillary exanthematous eruption similar to SDRIFE&#46;</p>"
        ]
      ]
      6 => array:8 [
        "identificador" => "fig0035"
        "etiqueta" => "Figure 7"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
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        "descripcion" => array:1 [
          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Livedoid rash with a transient course on the trunk of a patient with severe COVID-19&#46;</p>"
        ]
      ]
      7 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
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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="left" 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">Acral or Acroischemic Lesions&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">Vesicular and Chickenpox-Like Lesions&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">Urticarial Rash&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">Maculopapular Rash&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">Livedoid or Necrotic Lesions&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">Frequency&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">19&#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">9&#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">19&#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">47&#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">6&#37;&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">Site&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">Acral&#46; AsymmetricFeet &#62;hands5&#37; other sites&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">Trunk &#40;&#8764;100&#37;&#41;&#177;limbs &#40;&#8764;20&#37;&#41;No facial or mucosal involvement&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">Predominance on the trunk&#44; proximal to the limbs&#46;Symmetric&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">TrunkRegion proximal to the limbsNo mucosal involvement&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">Predominance of acral region and region distal to the legsRegions with greater hydrostatic pressure or lower regions&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">Symptoms&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">Asymptomatic &#40;&#8764;1&#47;3&#41;&#44; painful &#40;&#8764;1&#47;3&#41;&#44; or itchy &#40;&#8764;1&#47;3&#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">Mild or asymptomatic pruritus &#40;&#8764;2&#47;3&#41;&#44; pain or burning sensation&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">Almost constant pruritus&#44; of variable intensity&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">Pruritus &#40;&#62;2&#47;3&#41;&#44; mild to moderate&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">Pain&#44; burning&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">Characteristics&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">Macules&#44; papules&#44; plaques&#44; or nodulesErythematous to purpuric&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">Small-sized vesicles&#46; DisperseMonomorphic&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">Erythematous and edematous papules and plaques&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">Erythematous macules and papules&#44; often confluent&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">Ischemic or necrotic lesions&#44; often diffuse&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">Possible subtypes and variants&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">2 possible patterns&#58;&#8226; Pseudochilblain lesions &#40;&#62;70&#37;&#41; in the digital region&#46; Region distal from the fingers or toes&#46; Edematous&#46; Possible formation of vesicles&#44; pustules&#44; and scabs&#8226; Multiform erythema-like pattern &#40;approx&#46; 30&#37;&#41;&#46; Plaques &#40;heels&#41; and palms&#46; Erythematous&#44; confluent macules or papules&#44; with possible blistering&#46; No formation of typical targetoid lesions and less extensive than multiform erythema&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">&#8226; Generally&#44; disperse lesions&#46; Resemble other viral rashes&#8226; They may have hemorrhagic content&#44; be of larger size&#44; or show diffuse coverage of extensive areas&#8226; Less often&#44; predominantly acral vesicles or pustules&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">Cases have been reported of acral and facial involvement&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">Forms have been described with perifollicular predominance&#44; of the pityriasis rosea and flexural type that resemble SDRIFEIn some cases&#44; craniocaudal progression has been reported&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">From forms that resemble livedo reticularis or racemosa to areas of retiform purpura&#44; hemorrhagic blisters&#44; diffuse ischemia&#44; or gangrene involving the distal regions&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">Demographic profile&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">Adolescents or young adultsNo significant differences between sexes&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">Adults&#44; middle age &#40;30&#8211;40 years&#41;No significant differences between sexes&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">Adults&#44; middle age &#40;40&#8211;50 years&#41;No significant differences between sexes&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">Adults&#44; middle age &#40;30&#8211;50 years&#41;No significant differences between sexes&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">Middle aged and elderly adultsNo significant differences between sexes&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">Lag with respect to respiratory or systemic manifestations&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">Late onset&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">Early onset&#46; After a few days of respiratory and systemic manifestations &#40;15&#37; before other symptoms&#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">Early onset&#46; Accompanies respiratory or systemic manifestations&#44; or precedes them&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">Accompanies respiratory or systemic manifestations&#44; or appears a few days later&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">Accompanies respiratory or systemic manifestations&#44; or sometimes with late onset&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">Positive for PCR&#47;serology&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">&#60;50&#37; &#40;possibly associated with late onset&#41;In favor&#58; clinical and epidemiological evidence&#44; positive contacts&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">Frequent&#44; probably &#62;50&#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">Frequent&#44; probably &#62;50&#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">Frequent&#44; probably &#62;50&#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">Very frequent&#44; probably &#62;75&#37;&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">Mean duration &#40;days&#41; of the rash&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&#46;7 &#40;&#177;8&#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">10&#46;4 &#40;&#177;9&#46;3&#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">6&#46;8 &#40;&#177;7&#46;8&#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">8&#46;6 &#40;&#177;6&#46;8&#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">9&#46;4 &#40;&#177;5&#46;4&#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">Prognosis&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">It appears to be associated with milder disease &#40;acral ischemic lesions in patients with DIC are excluded from these cases&#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">Moderate severityRecovery without any scarring&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">VariableCases ranging from mild-moderate severity to death as the outcome &#40;2&#37; mortality&#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">Severe cases&#44; some with death as the outcome &#40;10&#37; mortality&#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">&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">Proposed treatments&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">Topical corticosteroids&#44; alone or in combination with topical antibiotics&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">Watch-and-wait&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">Oral antihistamines&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">Topical corticosteroids&#44; oral antihistamines&#44; oral corticosteroids&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">Support measuresAnticoagulation measures&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">Main references&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"><a class="elsevierStyleCrossRef" href="#bib0055">11</a>&#44;<a class="elsevierStyleCrossRefs" href="#bib0065">13&#8211;18</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"><a class="elsevierStyleCrossRef" href="#bib0055">11</a>&#44;<a class="elsevierStyleCrossRef" href="#bib0095">19</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"><a class="elsevierStyleCrossRef" href="#bib0055">11</a>&#44;<a class="elsevierStyleCrossRefs" href="#bib0105">21&#8211;23</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"><a class="elsevierStyleCrossRef" href="#bib0055">11</a>&#44;<a class="elsevierStyleCrossRef" href="#bib0125">25</a>&#44;<a class="elsevierStyleCrossRef" href="#bib0150">30</a>&#44;<a class="elsevierStyleCrossRef" href="#bib0155">31</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"><a class="elsevierStyleCrossRef" href="#bib0030">6</a>&#44;<a class="elsevierStyleCrossRef" href="#bib0170">34</a>&#44;<a class="elsevierStyleCrossRef" href="#bib0175">35</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                0 => "xTab2442599.png"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Characteristics of the Skin Manifestations Described in Association With SARS-Cov-2 Infection&#46;</p>"
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      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:35 [
            0 => array:3 [
              "identificador" => "bib0005"
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              "referencia" => array:1 [
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                  "contribucion" => array:1 [
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                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
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                        ]
                      ]
                    ]
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                  "host" => array:1 [
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                      "Revista" => array:5 [
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                        "fecha" => "2020"
                        "volumen" => "382"
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                      ]
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            1 => array:3 [
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              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Virology&#44; epidemiology pathogenesis&#44; and control of COVID-19"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
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                            0 => "Y&#46; Jin"
                            1 => "H&#46; Yang"
                            2 => "W&#46; Ji"
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                  "host" => array:1 [
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                      "Revista" => array:5 [
                        "tituloSerie" => "Viruses"
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            2 => array:3 [
              "identificador" => "bib0015"
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                  "contribucion" => array:1 [
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                        0 => array:2 [
                          "etal" => false
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                            1 => "J&#46;C&#46; Lebrato"
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                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:2 [
                        "fecha" => "2020"
                        "editorial" => "Ministerio de Sanidad"
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            3 => array:3 [
              "identificador" => "bib0020"
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                            0 => "M&#46;R&#46; Mehra"
                            1 => "S&#46;S&#46; Desai"
                            2 => "S&#46; Kuy"
                            3 => "T&#46;D&#46; Henry"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMc2021225"
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                        "tituloSerie" => "N Engl J Med"
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            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "5"
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                  "contribucion" => array:1 [
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
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                            1 => "O&#46; Vardeny"
                            2 => "T&#46; Michel"
                            3 => "J&#46;J&#46;V&#46; McMurray"
                            4 => "M&#46;A&#46; Pfeffer"
                            5 => "S&#46;D&#46; Solomon"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMsr2005760"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2020"
                        "volumen" => "382"
                        "paginaInicial" => "1653"
                        "paginaFinal" => "1659"
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32227760"
                            "web" => "Medline"
                          ]
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              "identificador" => "bib0030"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection&#58; a report of five cases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46; Magro"
                            1 => "J&#46;J&#46; Mulvey"
                            2 => "D&#46; Berlin"
                            3 => "G&#46; Nuovo"
                            4 => "S&#46; Salvatore"
                            5 => "J&#46; Harp"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.trsl.2020.04.007"
                      "Revista" => array:2 [
                        "tituloSerie" => "Transl Res"
                        "fecha" => "2020"
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            ]
            6 => array:3 [
              "identificador" => "bib0035"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical characteristics of coronavirus disease 2019 in China"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "W&#46;J&#46; Guan"
                            1 => "Z&#46;Y&#46; Ni"
                            2 => "Y&#46; Hu"
                            3 => "W&#46;H&#46; Liang"
                            4 => "C&#46;Q&#46; Ou"
                            5 => "J&#46;-X&#46; He"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa2002032"
                      "Revista" => array:7 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2020"
                        "volumen" => "382"
                        "paginaInicial" => "1708"
                        "paginaFinal" => "1720"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32109013"
                            "web" => "Medline"
                          ]
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Novelties in Dermatology
Cutaneous Manifestations in the Context of SARS-CoV-2 Infection (COVID-19)
Manifestaciones cutáneas en el contexto de la infección por SARS-CoV-2 (COVID-19)
J.M. Carrascosa
Corresponding author
jmcarrascosac@hotmail.com

Corresponding author.
, V. Morillas, I. Bielsa, M. Munera-Campos
Servicio de Dermatología, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Barcelona, Spain
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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 December 2019&#44; cases of pneumonia of unknown origin were reported in Wuhan&#44; China&#46; These were subsequently found to be caused by a new pathogen&#44; severe acute respiratory syndrome coronavirus 2 &#40;SARS-CoV-2&#41;&#44; isolated from the lower respiratory tract of affected patients&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">This is the third time in the last few decades that a coronavirus endemic in animal species has made the jump to humans&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Prior to these jumps&#44; coronaviruses &#40;HCoVs&#41; alfa &#40;HCoV-229E and HCoV-NL63&#41; and beta &#40;HCoV-JHKU1&#44; HCoV-OC43&#41; had been identified as endemic in humans&#46; In 2002&#44; there was an outbreak in China of a coronavirus that caused severe acute respiratory syndrome &#40;SARS&#41;&#46; The virus was named SARS-CoV&#44; and mortality was reported at around 10&#37;&#46; In 2012&#44; a respiratory syndrome caused by a coronavirus from the Middle East &#40;MERS-CoV&#41; was identified in Saudi Arabia&#46; In this case&#44; the mortality was 35&#37;&#46; SARS-CoV-2 is the new member of this group&#46; Disease associated with the virus is denoted coronavirus disease-19 &#40;COVID-19&#41;&#44; thus avoiding any geographical qualification&#46; The virus propagated out of control and the outbreak was declared a pandemic by the World Health Organization &#40;WHO&#41; in March 2020&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The most frequent manifestations of infection with SARS-CoV-2 include fever&#44; dry cough&#44; and dyspnea&#59; less frequent are odynophagia&#44; gastrointestinal symptoms&#44; and anosmia or ageusia&#46; A high proportion of patients develop pneumonia&#44; often bilaterally&#44; and this may lead to respiratory failure and the need for respiratory support in more than 6&#37; of cases&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Around 30&#37; will require admission to hospital&#44; and 5&#37; to 10&#37; will need admission to intensive care units &#40;ICUs&#41;&#46; Mortality varies widely&#44; from around 2&#37; to somewhat greater than 10&#37; in some countries&#44;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> and it appears higher in older individuals and those with comorbidities and marked respiratory compromise&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Infection can also occur without symptoms or with very mild symptoms&#44; and patients with these forms are probably potent vectors helping to spread infection&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Pathogenesis</span><p id="par0025" class="elsevierStylePara elsevierViewall">From the pathogenic point of view&#44; the immune response triggered by infection with SARS-CoV-2 may result in harmful effects&#44; such as endothelial cell dysfunction and activation of coagulation pathways&#59; this may explain the cardiovascular and thrombotic complications that affect a subgroup of patients&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The <span class="elsevierStyleItalic">corona</span> &#40;or crown&#41; of this virus is formed from protruding glycoproteins that form spikes&#46; These structures are what enables the virus to establish itself in the host&#46; The infection process occurs by binding to receptors of angiotensin converting enzyme 2 &#40;ACE2&#41;&#44; a membrane protein expressed in the cardiovascular system&#44; kidneys&#44; gastrointestinal system&#44; and lungs&#46; This enzyme is implicated in activation of the renin-angiotensin-aldosterone system &#40;RAAS&#41;&#46; ACE2&#44; in normal conditions&#44; counteracts the activity of the ACE enzyme by reducing the amount of angiotensin II &#40;vasoconstrictor&#41; and increasing the vasodilatory metabolites of the RAAS&#46; According to preliminary data&#44; when SARS-CoV-2 infection occurs&#44; ACE2 appears to be downregulated and this process is implicated in the development of acute lung lesions&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Contact between these 2 proteins &#40;spikes on the virus and ACE2&#41; permits anchoring via the transmembrane protease&#44; serine 2 &#40;TMPRSS2&#41; enzyme&#44; setting in motion a molecular cascade by which the virus is able to enter the cells&#46; The main target is the respiratory tract&#44; and&#44; in particular&#44; the alveoli&#44; where binding to the ACE2 receptors on pneumocytes occurs&#46; Alveolar epithelial cells and macrophages release proinflammatory cytokines that attract neutrophils and macrophages&#46; In normal conditions&#44; these are components of immune protection&#46; However&#44; in some patients&#44; the immune response is pathogenic or dysregulated&#44; with exaggerated release of IL-1&#946;&#44; IL-6&#44; and IFN-&#947;&#59; epithelial cell apoptosis&#59; and increased vascular permeability&#46; These events may lead to the development of SARS&#44; in which obliteration of the alveoli&#44; formation of typical hyaline membranes&#44; and hyperplasia of type II pneumocytes have been observed&#46; The terms coined for this exaggerated inflammation are <span class="elsevierStyleItalic">cytokine storm</span> or <span class="elsevierStyleItalic">cytokine release syndrome</span>&#46; Blood workup often shows lymphopenia&#44; with elevated values for inflammatory indicators &#40;C-reactive protein&#44; ferritin&#44; <span class="elsevierStyleSmallCaps">d</span>-dimer&#44; IL-6&#44; and procalcitonin&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">In addition&#44; the pattern of tissue damage observed in lung samples and some skin samples taken from patients with severe COVID-19 suggest occlusive microvascular damage mediated by complement activation of both the alternative pathway and the lectin-associated pathway&#46; Capillary damage has been found with extensive deposition of the C5b-9 membrane attack complex&#44; C4d&#44; and mannose-binding lectin-associated serine protease 2 &#40;MASP2&#41; in the lungs&#46; There have also been reports of a pattern of microvascular thrombotic disease mediated by complement in the skin of patients similar to that seen in livedo racemosa lesions and retiform purpura&#44; with C5b-9 and C4d deposition&#46; Activation of these mechanisms and interference in ACE2 function in target tissues due to viral action leads to an increase in angiotensin II&#44; associated with greater inflammation and oxidative stress&#46; The release of these reactive oxygen species and interference in antioxidant activity may increase complement activiation&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Skin Manifestations</span><p id="par0040" class="elsevierStylePara elsevierViewall">Articles published at the start of the pandemic in China considered skin manifestations as a minor and nonspecific sign&#44; with rash reported in 0&#46;2&#37; of patients&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> However&#44; this observation may presumably have been conditioned by the lack of dermatologists caring for patients affected by COVID-19 at the start of the outbreak&#46; Recalcati&#44;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> who was a dermatologist&#44; observed skin manifestations in 20&#46;4&#37; of a group of 88 patients with COVID-19&#59; in some cases&#44; these manifestations were present from the start whereas others appeared during or after admission to hospital&#46; Hedou et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> in response to the aforementioned article&#44; reported skin lesions attributable to COVID-19 in 4&#46;9&#37; of patients with a positive polymerase chain reaction &#40;PCR&#41; test result in a series of 103 patients&#46; However&#44; the real incidence of skin manifestations in infection by SARS-CoV-2 is not known&#44; bearing in mind that at the time&#44; the focus was on patients with severe signs or symptoms&#44; and diagnosis was made in many patients with no or limited symptoms following a telephone call by the patient to the primary care physician&#44; without any face-to-face visits&#44; and therefore no skin examination &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">Fern&#225;ndez-Nieto et al&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> reported difficulties facing dermatologists for taking samples and even clinical images in a pandemic that requires rigorous isolation measures&#44; and this is a barrier to conducting reliable epidemiological studies&#46; For these procedures&#44; transparent bags can be considered both for transporting photographic equipment and the tools necessary for taking biopsies&#46; The COVID-19 pandemic represents a completely new scenario for dermatologists&#44; and this situation may be prolonged&#44; depending on how the pandemic progresses&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The recent article by Galv&#225;n et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> supported by the Spanish Academy of Dermatology and Venereology &#40;AEDV&#41;&#44; reported heterogeneous and complex skin manifestations associated with COVID-19 infection&#46; The authors studied a group of 375 patients prospectively enrolled in several Spanish hospitals for 2 weeks during the peak of the pandemic&#46; They identified 5 main clinical patterns related to COVID-19&#58; acral areas of erythema with vesicles or pustules &#40;pseudochilblain pattern&#41; &#40;19&#37;&#41;&#44; vesicular rashes &#40;9&#37;&#41;&#44; urticarial lesions &#40;19&#37;&#41;&#44; maculopapular lesions &#40;47&#37;&#41;&#44; and livedo or necrosis &#40;6&#37;&#41;&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The following paragraphs describe the most important clinical features and diagnostic and prognostic implications in patients with SARS-CoV-2 infection&#46;</p><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Acral or Acroischemic Lesions</span><p id="par0060" class="elsevierStylePara elsevierViewall">The acral pseudochilblain pattern of lesions&#44; reported by Galv&#225;n et al&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> as acral&#44; erythematous&#44; and edematous lesions&#44; with formation of vesicles and pustules&#44; are perhaps the most characteristic skin lesions associated with the SARS-CoV-2 pandemic&#46; The description and reporting of these lesions initially occurred outside academic circles in an informal fashion in medical or dermatological social media&#44; based on shared images from family members&#44; acquaintances&#44; and colleagues&#46; The first case published reported an adolescent aged 13 years who developed purpuric lesions on the feet prior to developing systemic symptoms such as fever&#44; muscle pain&#44; and headache&#44; in a family with suspected cases of COVID-19 infection at the time the pandemic in Italy was spreading rapidly&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> However&#44; no specific microbiological studies were performed&#46; In the article&#44; the authors mentioned the existence of an epidemic of similar lesions in children with suspected COVID-19 in Italy&#46; In the series by Galv&#225;n et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> the pattern of pseudochilblain lesions was the second most common skin manifestation &#40;19&#37;&#41;&#46; They developed in young patients&#44; generally late on in the course of the disease&#44; and were present for a period of 12&#46;7 days&#44; in general&#44; in patients with mild disease or asymptomatic individuals&#46; These lesions were described as painful &#40;32&#37;&#41; or itchy &#40;30&#37;&#41;&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">From the clinical point of view&#44; the pseudochilblain pattern of lesions consists of macules&#44; papules&#44; or plaques&#44; often about a millimeter in size&#44; and usually with a clearly defined border in the metatarsophalangeal area&#44; although the whole of the finger or toe can be involved &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Often&#44; only some fingers or toes are affected while others completely lack any involvement&#44; and at times&#44; these lesions may be accompanied by lesions in the palmar and plantar region&#46; They usually affect the feet and&#44; to a lesser degree&#44; the hands&#46; Initially purpuric or bluish&#44; they can form blisters or scabs during the course of the disease&#59; at times&#44; they may resemble multiform erythema<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> or vasculitis&#59; in fact&#44; some authors recognize a multiform erythema type subgroup&#44;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#8211;15</span></a> with targetoid or atypical target lesions&#44; which can be associated with lesions in extensor areas&#44; such as the elbows&#46; In cases with histological study&#44; a lymphocytic infiltrate is reported in the superficial and deep dermis&#44; of perivascular predominance&#44; occasionally associated with edema and signs of endothelial activation&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Keratinocyte necrosis and perieccrine reinforcement may be present&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">Alramthan and Aldaraji&#44;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> reporting 2 clinical cases in young adults&#44; proposed the hypothesis&#44; not confirmed with histology in their own cases&#44; that formation of hyaline thrombi in small caliber vessels of different organs observed in autopsies of patients could explain the pseudochilblain characteristics of the lesions&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Fewer than half the cases had microbiological or serological test results available &#40;specific PCR or rapid antibody test for IgM&#47;IgG&#41;&#46; In general&#44; when assessed&#44; laboratory abnormalities or elevations have generally been lacking in measures of inflammation such as D-dimer&#44; C reactive protein &#40;CRP&#41;&#44; or lactate dehydrogenase &#40;LDH&#41;&#44; indicative of poor prognosis for this disease&#46; The strongest evidence of association with viral infection was therefore that presentation occurred during the pandemic &#40;and in a different context to that of chilblains&#44; in the warmer months than when they usually appear&#41; and a history in the family environment or personal situation consistent with infection&#46; The authors suggested these negative results were due to the late development of these lesions in the course of the disease&#59; the low sensitivity of the tests used&#44; which has led to mass recall of some batches&#59; and the rapid disappearance of antibodies&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;15</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Docampo-Sim&#243;n et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> in the first prospective study of skin manifestations&#44; found a positive PCR result in only 1 of the 38 samples tested&#46; In addition&#44; due to the aforementioned technical reasons &#40;time since infection&#44; false negatives&#41;&#44; the authors considered the possibility that this manifestation simply has nothing to do with COVID-19&#46; Other possible explanations could be a traumatic origin during lock-down or even the concurrent expansion of another virus&#44; such as parvovirus B19&#46; This possible relation with the lock-down period&#44; and not necessarily with COVID-19&#44; has also been suggested in a recent series with similar results&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">During the worst weeks of the pandemic&#44; we saw patients with these characteristics almost on a daily basis in our clinics&#46; From both the clinical and epidemiological point of view&#44; the characteristics are consistent with those described above&#46; Most of our patients were young&#44; asymptomatic or with mild symptoms&#44; and not one of them had a serious complication associated with COVID-19&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Vesicular and Chickenpox-Like Lesions</span><p id="par0090" class="elsevierStylePara elsevierViewall">In 8 Italian centers&#44; clinical data were collected from patients with COVID-19&#44; with microbiological confirmation by RT-PCR from a nasopharyngeal swab and with no history of medications that could have triggered chickenpox-like lesions&#46; In total&#44; the study included 22 patients&#44; mainly males&#44; with a mean age of 60 years&#46; The lag from the onset of symptoms of COVID-19 to development of skin manifestations was relatively short&#44; 3 days &#40;range&#44; 2 to 12 days&#41;&#46; Most patients presented with the full clinical manifestations of the disease&#44; with general and respiratory manifestations&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">Vesicular lesions&#44; usually monomorphic&#44; appear early on and may at times precede other symptoms &#40;in 15&#37; of patients&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> although in most cases&#44; up to 79&#46;2&#37; in a series of 24 patents reported by Fernandez-Nieto et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> they occur at the onset of other symptoms&#46; There is involvement of the trunk in almost all cases and in 20&#37; the limbs are also affected &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; Exceptionally&#44; facial and mucosal involvement have been reported&#46; The skin lesions are barely symptomatic&#44; but when they do cause symptoms&#44; these are usually mild itching and&#44; to a lesser extent pain or burning sensation&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;19</span></a> Although the lesions may be disperse&#44; an extensive disseminated pattern is more frequent&#44; 75&#37; according to Fernandez-Nieto et al&#46; In some patients&#44; the legs may be affected&#44; or the lesions may present with hemorrhagic content or be large&#44; with a diffuse distribution&#46; The mean duration of skin symptoms is 10&#46;4 days &#40;&#177;9&#46;3&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> In cases in which a biopsy was obtained&#44; the findings were described as consistent with viral infection&#44; showing vacuolar abnormalities and abnormal maturation of keratinocytes&#44; as well as larger&#44; multinucleated keratinocytes&#44; and dyskeratosis&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> There have been no reports of presence of SARS-Cov-2 confirmed with positive PCR in biopsies of skin lesions&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Urticarial Rash</span><p id="par0100" class="elsevierStylePara elsevierViewall">Henry et al&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> reported the case of a female patient who developed an urticarial rash&#44; accompanied by odynophagia and arthralgia&#44; before developing the full clinical manifestations of COVID-19&#46; Van Damme et al&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> reported a further 2 cases of urticarial rash as the first clinical manifestation of COVID-19&#44; although microbiological confirmation of infection was only obtained in 1 of those&#44; and in both cases the skin manifestations preceded pyrexia&#46; One of the patients developed severe respiratory failure&#44; leading to death&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Urticarial rash accounts for 19&#37; of skin manifestations in COVID-19&#46; In general&#44; these skin manifestations become evident more or less at the same time as other general and respiratory symptoms&#46; Lesions occur predominantly on the trunk&#44; and involvement of the face and hands is frequent&#44; with resolution in approximately 7 days&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> In one of the cases reported&#44; histological study showed edema of the upper dermis and perivascular lymphocytic infiltration&#44; with some eosinophils present&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Although such lesions may be associated with worse prognosis in some patients&#44;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> this is a nonspecific rash&#44; and it has been reported in patients with a favorable clinical outcome and those with limited symptoms&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">There is probably a certain degree of variability in the way in which rashes are reported as urticarial maculopapular because&#44; in the cases described&#44; it is not specified whether the lesions follow a transient course or not&#46; These are nonspecific rashes in which it is difficult to establish a solid relationship with viral infection&#44; bearing in mind that the patients who present with these lesions have often received a range of treatments such as antiviral agents&#44; antibiotics&#44; hydroxychloroquine&#44; anticoagulants&#44; and support treatments&#44; and these could also trigger skin reactions &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; In fact&#44; in a histological study&#44; some cases of vacuolar interface dermatitis were observed with occasional necrotic keratinocytes&#44; findings more reminiscent of a multiform erythematous pattern&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Maculopapular Rash</span><p id="par0115" class="elsevierStylePara elsevierViewall">This group of lesions includes a heterogeneous group of rashes that&#44; considered together&#44; and given the difficulty of further subclassification&#44; account for 47&#37; of the skin manifestations in patients with COVID-19&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> At times&#44; these rashes may be accompanied by a petechial component or with macules or more extensive areas with a purpuric appearance&#46; In other cases&#44; the lesions have a markedly perifollicular distribution &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41; with variable degrees of scaling&#44; some of which have been reported as similar to pityriasis rosea&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> Infiltrated papules have also been observed&#59; these are pseudovesicular lesions or similar to erythema elevatum diutinum or multiform erythema&#44; and they may occasionally be pruritic &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> A markedly craniocaudal development has also been reported&#44; with involvement of the folds but without the palmoplantar region or the mucosa being affected&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">27&#44;28</span></a></p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><elsevierMultimedia ident="fig0025"></elsevierMultimedia><p id="par0120" class="elsevierStylePara elsevierViewall">Jimenez-Cauhe et al&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> reported the case of a female patient who developed a coalescent erythematous-purpuric rash about a millimeter in size&#44; with a flexural distribution predominantly in the periaxillary region&#46; The authors considered the difficulty of associating the skin manifestations with viral infection in view of its nonspecific appearance and concomitant medication use&#46; Other authors have reported the appearance of rash that resembles the typical skin involvement of symmetrical drug-related intertriginous and flexural exanthema &#40;SDRIFE&#41;&#44; possibly associated with viral infection&#44; given that the rash resolved despite continued use of the drug&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> We have also observed a similar distribution in our own patients &#40;<a class="elsevierStyleCrossRef" href="#fig0030">Fig&#46; 6</a>&#41;&#46; From the histological point of view&#44; a range of features have been reported within the group of maculopapular rashes&#44; such as a perivascular inflammatory infiltrate with discrete lymphocytic exocytosis&#44; marked vessel dilatation in the superficial and medial dermis&#44; as well as lymphocytic vasculitis&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">31&#44;32</span></a></p><elsevierMultimedia ident="fig0030"></elsevierMultimedia><p id="par0125" class="elsevierStylePara elsevierViewall">There is limited additional information in these patients regarding the timing with respect to other clinical manifestations or its prognostic or diagnostic value&#46; In most cases&#44; maculopapular rashes appear either at the same time as the characteristic respiratory symptoms or a few days later&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;28&#44;32&#44;33</span></a> However&#44; in our hospital&#44; we have detected more or less generalized maculopapular rashes&#44; in some cases similar to multiform erythema&#44; in young patients with a history of mild or even no symptoms&#44; although with epidemiological evidence of infection with SARS-CoV-2 and these resemble those that can be seen in other viral infections&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Livedoid or Necrotic Lesions</span><p id="par0130" class="elsevierStylePara elsevierViewall">Livedoid or necrotic lesions are relatively uncommon&#44; accounting for 6&#37; of skin lesions in the series reported by Galv&#225;n et al&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> These are lesions usually reported in elderly patients with prior comorbidities and with severe forms of COVID-19 infection&#46; They are considered secondary to vascular micro-occlusion and acral ischemia due to general deterioration in the patient&#39;s state and&#47;or the coagulation disorders attributed to COVID-19<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;5</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0035">Fig&#46; 7</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> However&#44; in some patients&#44; episodes have been reported of patchy livedo reticularis that presented over the course of minutes or hours&#44; of an uncertain nature and a benign course&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a></p><elsevierMultimedia ident="fig0035"></elsevierMultimedia><p id="par0135" class="elsevierStylePara elsevierViewall">In the histological study of cutaneous purpuric lesions&#44; a pauci-inflammatory thrombogenic vasculopathy has been found&#44; with C5b-9 and C4d deposits&#44; and localization of viral particles&#44; leading to suspicion of the presence of a catastrophic microvascular lesion caused by complement activation&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conclusions</span><p id="par0140" class="elsevierStylePara elsevierViewall">The SARS-CoV-2 pandemic has had a major impact from the healthcare&#44; economic&#44; and societal point of view&#44; and will probably lead to lasting changes in our generation&#46; Considered initially as of little relevance&#44; the dermatological manifestations have proved to be varied and complex&#46; Recent efforts to characterize cutaneous involvement in patients with COVID-19&#44; implemented in a study conducted quickly and rigorously in a full health emergency&#44; has identified 5 main groups of lesion &#40;acral&#44; vesicular&#44; urticarial&#44; maculopapular and livedoid&#47;necrotic lesions&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> Although these manifestations are considered a reflection of different pathogenic pathways&#44; with a variable implication of the viral infection&#44; inflammatory processes&#44; and vascular and systemic complications of the disease&#44; there is a substantial knowledge gap in many aspects&#46; Thus&#44; it cannot be ruled out that acral lesions&#44; reported as characteristic given the epidemiological evidence rather than microbiological tests in most cases&#44; may not be directly related to COVID-19&#46; Extensive urticarial or maculopapular rashes&#44; often described in symptomatic or even hospitalized patients&#44; may be linked in many cases to drugs able to trigger them&#44; such as hydroxychloroquine or antibiotics&#44; administered during the COVID-19 pandemic despite limited evidence of their effectiveness&#46; Finally&#44; the heterogeneous set of maculopapular rashes consistent with viral infection&#44; multiform erythema&#44; or SDRIFE&#44; may be associated with other etiologic agents neglected during the pandemic&#44; as in many cases&#44; microbiological or serologic confirmation of SARS-CoV-2 infection is lacking&#46; Thus&#44; in the panorama of lesions associated with COVID-19&#44; for the most part&#44; priority in the international literature during the peak of the pandemic was given to rapid publication&#44; even though the description&#44; support&#44; or methodological rigor were not ideal&#46; Familiarity with the skin manifestations may allow not only greater investigation into aspects still little known in COVID-19&#44; but also may help a more rapid diagnosis and even serve as a prognostic marker&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Conflicts of Interest</span><p id="par0145" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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              "titulo" => "Acral or Acroischemic Lesions"
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              "titulo" => "Vesicular and Chickenpox-Like Lesions"
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              "titulo" => "Urticarial Rash"
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              "titulo" => "Maculopapular Rash"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">The coronavirus 2019 &#40;COVID-19&#41; pandemic&#44; caused by severe acute respiratory syndrome coronavirus 2 &#40;SARS-CoV-2&#41;&#44; has had enormous health&#44; economic&#44; and social consequences&#46; The clinical spectrum of cutaneous manifestations observed in patients with COVID-19 is both heterogeneous and complex&#46; To date&#44; reports have identified 5 main categories&#58; acral lesions&#44; vesicular rashes&#44; urticarial rashes&#44; maculopapular rashes&#44; and livedoid and necrotic lesions&#46; However&#44; these will probably be modified as new information comes to light&#46; Cutaneous manifestations associated with COVID-19 probably reflect the activation of pathogenic pathways by the virus or a response to inflammatory processes&#44; vascular or systemic complications&#44; or even treatments&#46; Familiarity with the cutaneous manifestations of COVID-19 may enable early diagnosis or help guide prognosis&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">La pandemia por SARS-CoV-2 ha causado un gran impacto desde el punto de vista sanitario&#44; econ&#243;mico y social&#46; La semiolog&#237;a dermatol&#243;gica se ha demostrado heterog&#233;nea y compleja&#46; En la actualidad se han definido cinco grupos principales de manifestaciones cut&#225;neas asociadas a la COVID-19&#58; lesiones acrales&#44; exantemas vesiculares&#44; erupciones urticariales&#44; exantemas maculopapulares y lesiones livedoides&#47;necr&#243;ticas&#46; Sin embargo&#44; es probable que esta clasificaci&#243;n se modifique en el futuro&#46; La cl&#237;nica cut&#225;nea es probablemente el reflejo de distintas v&#237;as patog&#233;nicas con implicaci&#243;n variable de la infecci&#243;n v&#237;rica&#44; del proceso inflamatorio&#44; de las complicaciones vasculares o sist&#233;micas de la enfermedad o incluso de los tratamientos administrados&#46; El conocimiento de las manifestaciones cut&#225;neas puede permitir un diagn&#243;stico precoz o incluso servir como marcador pron&#243;stico&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Carrascosa JM&#44; Morillas V&#44; Bielsa I&#44; Munera-Campos M&#46; Manifestaciones cut&#225;neas en el contexto de la infecci&#243;n por SARS-CoV-2 &#40;COVID-19&#41;&#46; Actas Dermosifiliogr&#46; 2020&#46; <span class="elsevierStyleInterRef" id="intr0005" href="https://doi.org/10.1016/j.ad.2020.08.002">https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1016&#47;j&#46;ad&#46;2020&#46;08&#46;002</span></p>"
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            "identificador" => "at0040"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "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="left" 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">Acral or Acroischemic Lesions&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">Vesicular and Chickenpox-Like Lesions&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">Urticarial Rash&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">Maculopapular Rash&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">Livedoid or Necrotic Lesions&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">Frequency&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">19&#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">9&#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">19&#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">47&#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">6&#37;&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">Site&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">Acral&#46; AsymmetricFeet &#62;hands5&#37; other sites&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">Trunk &#40;&#8764;100&#37;&#41;&#177;limbs &#40;&#8764;20&#37;&#41;No facial or mucosal involvement&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">Predominance on the trunk&#44; proximal to the limbs&#46;Symmetric&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">TrunkRegion proximal to the limbsNo mucosal involvement&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">Predominance of acral region and region distal to the legsRegions with greater hydrostatic pressure or lower regions&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">Symptoms&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">Asymptomatic &#40;&#8764;1&#47;3&#41;&#44; painful &#40;&#8764;1&#47;3&#41;&#44; or itchy &#40;&#8764;1&#47;3&#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">Mild or asymptomatic pruritus &#40;&#8764;2&#47;3&#41;&#44; pain or burning sensation&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">Almost constant pruritus&#44; of variable intensity&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">Pruritus &#40;&#62;2&#47;3&#41;&#44; mild to moderate&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">Pain&#44; burning&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">Characteristics&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">Macules&#44; papules&#44; plaques&#44; or nodulesErythematous to purpuric&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">Small-sized vesicles&#46; DisperseMonomorphic&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">Erythematous and edematous papules and plaques&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">Erythematous macules and papules&#44; often confluent&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">Ischemic or necrotic lesions&#44; often diffuse&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">Possible subtypes and variants&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">2 possible patterns&#58;&#8226; Pseudochilblain lesions &#40;&#62;70&#37;&#41; in the digital region&#46; Region distal from the fingers or toes&#46; Edematous&#46; Possible formation of vesicles&#44; pustules&#44; and scabs&#8226; Multiform erythema-like pattern &#40;approx&#46; 30&#37;&#41;&#46; Plaques &#40;heels&#41; and palms&#46; Erythematous&#44; confluent macules or papules&#44; with possible blistering&#46; No formation of typical targetoid lesions and less extensive than multiform erythema&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">&#8226; Generally&#44; disperse lesions&#46; Resemble other viral rashes&#8226; They may have hemorrhagic content&#44; be of larger size&#44; or show diffuse coverage of extensive areas&#8226; Less often&#44; predominantly acral vesicles or pustules&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">Cases have been reported of acral and facial involvement&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">Forms have been described with perifollicular predominance&#44; of the pityriasis rosea and flexural type that resemble SDRIFEIn some cases&#44; craniocaudal progression has been reported&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">From forms that resemble livedo reticularis or racemosa to areas of retiform purpura&#44; hemorrhagic blisters&#44; diffuse ischemia&#44; or gangrene involving the distal regions&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">Demographic profile&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">Adolescents or young adultsNo significant differences between sexes&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">Adults&#44; middle age &#40;30&#8211;40 years&#41;No significant differences between sexes&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">Adults&#44; middle age &#40;40&#8211;50 years&#41;No significant differences between sexes&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">Adults&#44; middle age &#40;30&#8211;50 years&#41;No significant differences between sexes&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">Middle aged and elderly adultsNo significant differences between sexes&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">Lag with respect to respiratory or systemic manifestations&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">Late onset&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">Early onset&#46; After a few days of respiratory and systemic manifestations &#40;15&#37; before other symptoms&#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">Early onset&#46; Accompanies respiratory or systemic manifestations&#44; or precedes them&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">Accompanies respiratory or systemic manifestations&#44; or appears a few days later&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">Accompanies respiratory or systemic manifestations&#44; or sometimes with late onset&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">Positive for PCR&#47;serology&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">&#60;50&#37; &#40;possibly associated with late onset&#41;In favor&#58; clinical and epidemiological evidence&#44; positive contacts&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">Frequent&#44; probably &#62;50&#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">Frequent&#44; probably &#62;50&#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">Frequent&#44; probably &#62;50&#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">Very frequent&#44; probably &#62;75&#37;&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">Mean duration &#40;days&#41; of the rash&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&#46;7 &#40;&#177;8&#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">10&#46;4 &#40;&#177;9&#46;3&#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">6&#46;8 &#40;&#177;7&#46;8&#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">8&#46;6 &#40;&#177;6&#46;8&#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">9&#46;4 &#40;&#177;5&#46;4&#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">Prognosis&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">It appears to be associated with milder disease &#40;acral ischemic lesions in patients with DIC are excluded from these cases&#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">Moderate severityRecovery without any scarring&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">VariableCases ranging from mild-moderate severity to death as the outcome &#40;2&#37; mortality&#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">Severe cases&#44; some with death as the outcome &#40;10&#37; mortality&#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">&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">Proposed treatments&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">Topical corticosteroids&#44; alone or in combination with topical antibiotics&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">Watch-and-wait&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">Oral antihistamines&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">Topical corticosteroids&#44; oral antihistamines&#44; oral corticosteroids&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">Support measuresAnticoagulation measures&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">Main references&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"><a class="elsevierStyleCrossRef" href="#bib0055">11</a>&#44;<a class="elsevierStyleCrossRefs" href="#bib0065">13&#8211;18</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"><a class="elsevierStyleCrossRef" href="#bib0055">11</a>&#44;<a class="elsevierStyleCrossRef" href="#bib0095">19</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"><a class="elsevierStyleCrossRef" href="#bib0055">11</a>&#44;<a class="elsevierStyleCrossRefs" href="#bib0105">21&#8211;23</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"><a class="elsevierStyleCrossRef" href="#bib0055">11</a>&#44;<a class="elsevierStyleCrossRef" href="#bib0125">25</a>&#44;<a class="elsevierStyleCrossRef" href="#bib0150">30</a>&#44;<a class="elsevierStyleCrossRef" href="#bib0155">31</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"><a class="elsevierStyleCrossRef" href="#bib0030">6</a>&#44;<a class="elsevierStyleCrossRef" href="#bib0170">34</a>&#44;<a class="elsevierStyleCrossRef" href="#bib0175">35</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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        "texto" => "<p id="par0150" class="elsevierStylePara elsevierViewall">We would like to thank Doctors Aram Boada&#44; Isabel Bielsa&#44; Mar&#237;a Blanco&#44; Ferran Ballesc&#224;&#44; Juli Bassas&#44; Elena del Alc&#225;zar&#44; Gonzalo Castillo&#44; Carlos Ferr&#225;ndiz&#44; Mar&#237;a Jos&#233; Fuente&#44; Adri&#224; Plana&#44; Nina Richarz&#44; Ver&#243;nica Mora&#44; Arantxa Arrieta&#44; and Ane Jaka&#44; with whom the authors have worked and shared knowledge during the peak of the COVID-19 pandemic&#46;</p>"
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Article information
ISSN: 15782190
Original language: English
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Idiomas
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