Cutaneous and histopathological features of coronavirus disease 2019 in pediatrics: A review article

Prevalence of dermatological manifestations of coronavirus disease 2019 (COVID‐19) is estimated between 0.25% and 3% in children and adolescents. In this review article, we decided to describe the cutaneous and histopathological manifestations of COVID‐19 infection in pediatrics. We searched published articles in PubMed database for key words of “children” or “pediatric” and “cutaneous” or “dermatology” or “skin” and “COVID‐19” or “SARS‐CoV‐2” or “Coronavirus disease 2019” in abstract or title from December of 2019 until September 2020. Finally, 38 articles were selected. The majority of patients were between 11 and 17 years old with predominantly male gender. Most of the patients were either asymptomatic or had a few general symptoms. The latency time from appearance of general symptoms to cutaneous ones was between 1 day and weeks. Skin lesions faded between 3 and 88 days without any sequelae, spontaneously or with either topical or systemic corticosteroids. Skin manifestations were chilblain‐like (pseudochilblain), erythema multiforme‐like, dactylitis, acral erythema, acute urticaria, livedo reticularis, mottling, acro‐ischemia, generalized maculopapular lesions, eyelid dermatitis, miliaria‐like, varicelliform lesions, and petechiae and/or purpura. Kawa‐COVID‐19 patients were presented more frequently with cardiogenic shock, neurological symptoms, lymphocytopenia, and thrombocytopenia as compared to classic Kawasaki's disease. Furthermore, more number of cases were resistant to the first‐line treatments.     

The clinics of HHV‐6 infection in COVID‐19 pandemic: Pityriasis rosea and Kawasaki disease

A new type of coronavirus family (SARS‐CoV‐2), which can be found in humans and animals, with many varieties and clinical symptoms, was first seen in Wuhan, China in late 2019, under the name novel Coronavirus Disease 2019 (COVID‐19). In the literature, cutaneous symptoms related to the disease are generally emphasized. However, it is not yet known whether this new SARS‐CoV‐2 virus, which has entered our lives, plays a role in the etiopathogenesis of dermatological diseases. The patients who were admitted to the dermatology outpatient clinic between 1 April and 15 May 2019, and on 1 April and 15 May 2020 were retrospectively analyzed by searching the hospital automation system and patient files. The reason for the same months to be included in the study was to exclude seasonal effects on the diseases. After pandemic, the number of patients with Pityriasis rosea and Kawasaki disease increased significantly in patients who applied to the dermatology outpatient clinic. Our study is the first study showing Pityriasis rosea increase during the pandemic period. We think that this increase is related to HHV‐6 reactivation. Herein, we wanted to draw attention to two diseases in which Human Herpes 6 (HHV‐6) was accused in etiopathogenesis: Kawasaki disease and Pityriasis rosea.     

Which dermatology patients attend to Dermatology Outpatient Clinics during the SARS‐CoV‐2 outbreak in Turkey and what happened to them?

Coronavirus disease, first emerged in Wuhan, rapidly spread all over the world since December 2019. There are concerns about elective dermatology appointments and its results. Herein, we aimed to find out which type of dermatologic patients attended to dermatology outpatient clinic. The patients visiting the clinics for elective dermatologic diseases between March 11 and 18, 2020, were included in this study. Their age, sex, diagnosis of disease, requirement for emergent intervention, and their medical records about COVID‐19 were obtained. There were 390 patients attending to the dermatology outpatient clinic in this period. The most common disease was acne (N: 94, 24%), only 19% of patients need emergent interventions or dose adjustment. There were 40 (10%) patients over the age of 65. After their visits, five patients were diagnosed as COVID‐19 in 2weeks. Dermatologic examinations may be a vector for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) transmission since being closed to the patient. Five of our patients were diagnosed as COVID‐19 after their elective visit to hospital. Since the asymptomatic course of some young patients, most of our patients were not screened for COVID‐19. Our findings support the concerns of elective physician examinations.     

Six months into the pandemic. A review of skin manifestations in SARS‐CoV‐2 infection

During the COVID‐19 pandemic, various cutaneous manifestations have been described as associated with SARS‐CoV2 infection. It is debated if skin lesions could represent a diagnostic or prognostic indicator. Specifically, it is unclear whether skin lesions may be used to perform an early diagnosis and/or to predict worse outcomes. In this review, we described the cutaneous signs so far reported as COVID‐19‐related and discussed their incidence, clinico‐pathological features, and diagnostic and prognostic value.     

Novel coronavirus disease 2019 (COVID‐19) and neurodegenerative disorders

During the last few months, the whole humanity is experiencing largest and most severe sudden influx of COVID‐19 outbreak caused by the novel coronavirus (CoV) originated from Wuhan, China. According to the WHO reports, total 3 862 676 positive cases and 265 961 deaths have been recorded worldwide due to COVID‐19 infection as of May 9, 2020. CoVs are a large family of viruses (enveloped, single‐stranded RNA viruses), which includes severe acute respiratory syndrome coronavirus (SARS‐CoV) and Middle East respiratory syndrome‐related coronavirus (MERS‐CoV). New SARS CoV2 is the members of Betacoronavirus genus. These viruses cause infections in bats, camels and humans, and a few other associated species. Despite many neurologic complications associated with SARS‐CoV‐2 infection, it is still unclear whether these symptoms results from direct neural injury or due to some other reason. Currently, it appears that most of the neurological symptoms of COVID‐19 are nonspecific and secondary to the systemic illness. A single case of acute hemorrhagic necrotizing encephalopathy has been reported. SARS‐CoV‐2 associated Guillain‐Barré syndrome is an atypical case. Till today, no convincing evidence is available to confirm that the SARS‐CoV‐2 virus directly affects nerves system in humans. However, postinfection surveillance will be necessary to identify the possible post‐COVID‐19 neurologic syndromes.     

Cutaneous manifestations of the Coronavirus Disease 2019 (COVID‐19): A brief review

COVID‐19, first appeared in December 2019 in Wuhan, China, has been spreading quickly throughout the world. We reviewed the evidence on cutaneous manifestations of COVID‐19 based on PubMed database. The searching strategy was (COVID* or coronavirus*) and (dermatol* or skin* or cutaneous*). The publication time was limited to 2019 onward. After independent review by two authors, 14 studies with 228 confirmed cases were included in the analysis. A total of 60 patients developed skin rashes, and the age ranged from 8 to 84. Exanthematous eruptions potentially related to COVID‐19 infection were highly variable and heterogeneous. Skin lesions mainly appeared erythematous, urticarial, and vesicular (chicken pox‐like or varicelliform). Petechiae rash, livedo reticularis, and reactivation of oral HSV‐1 were also observed in single cases. Newly reported eruptions like vascular lesions and peculiar (perniosis‐like) skin lesions caused concern among dermatologists. Exanthems were widely distributed and were primarily located on the trunk. Associated symptoms, latency time, treatment, and prognosis were also carefully summarized. This study reviewed the recently published COVID‐19 studies with skin manifestations, which may pave the way for further research.     

Dupilumab and COVID‐19: What should we expect?

Coronavirus disease 2019 (COVID‐19) is a pandemic disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) with high morbidity and mortality. There are very limited data on the interference of immunomodulating drugs on the risk of infection and on the course of the disease. In particular, there are no current clinical data about the interference exerted by dupilumab, a biologic drugs blocking IL‐4 and IL‐13, used for adult atopic dermatitis. The pathogenesis of COVID‐19 is complex, characterized by an immune response mainly Th1/Th17. The hyper‐activation of these cells may cause the release of pro‐inflammatory cytokines that may result in lung impairment. IL‐4 and IL‐13 are Th2 cytokines, thus being part of a pathway not considered implicated in host defense mechanism against viral infections. Indeed, viral infections, including respiratory infections, have not been reported as a significant adverse event in clinical trials. Furthermore, dupilumab has been proved to be efficacious also in exacerbations of asthma, and it is known that viral infections can worsen asthma. Therefore, the current data seem to suggest that treatment with dupilumab should not be stopped during COVID‐19 pandemic. Obviously, a careful assessment is mandatory for each individual patient and further studies are necessary to characterize the immunologic responses in COVID‐19.     

Suspected COVID‐19‐related reticulated purpura of the soles in an infant

A growing number of skin lesions during the COVID‐19 pandemic are being recognized. Acral ischemic lesions identical to chilblains are most typical in children and young adults. We report an infant girl, aged 1 month and 29 days, with a peculiar reticulated purpuric eruption on her soles, with positive immunohistochemistry for SARS‐CoV‐2 in the endothelia of dermal blood vessels. The patient had an excellent outcome without specific therapy.     

Coronavirus disease (COVID‐19): An updated review based on current knowledge and existing literature for dermatologists

The world entered the year 2020 with reports of the emergence of a new viral illness in Wuhan city, Hubei province, China. In January 2020, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) was identified to be the causative novel coronavirus for the cluster of patients suffering from pneumonia in China. The disease was later named as coronavirus disease (COVID‐19) and was declared a pandemic by the World Health Organization on March 11, 2020. Several studies, since then, have tried to study and explain the origin of SARS‐CoV‐2, its structure and pathogenicity, epidemiology, modes of transmission, spectrum of illness and causes of mortality and morbidity. The current management strategies focus on supportive care and prevention of complications. With no definite treatment, as of now, encouraging reports of some anti‐viral and anti‐malarial drugs in the management of COVID‐19 generate some hope. This review intends to cover the current known aspects of COVID‐19 and SARS‐CoV‐19, based on the available literature.     

Tetracyclines in COVID‐19 patients quarantined at home: Literature evidence supporting real‐world data from a multicenter observational study targeting inflammatory and infectious dermatoses

Tetracyclines (TetraC) are widely used in dermatology for both inflammatory and infectious dermatoses; recently both in vivo and in vitro studies started to suggest also a potential antiviral effect. During COVID‐19 outbreak, several dermatological patients contracted SARS‐CoV‐2 experiencing only mild symptoms, but no protocol were approved. A multicenter prospective observational study that enrolled COVID‐19 patients visited with teledermatology and undergoing TetraC was performed. About 38 adult outpatients (M/F: 20/18, age 42.6 years [21‐67]) were enrolled. During the TetraC treatment, symptoms resolved in all patients within 10 days. Remarkably, ageusia and anosmia disappeared in the first week of TetraC treatment. TetraC seem a promising drug to treat COVID‐19 outpatients with mild symptoms.     

From dermatological conditions to COVID‐19: Reasoning for anticoagulation,suppression of inflammation,and hyperbaric oxygen therapy

COVID‐19 generates a complex systemic inflammatory response that can lead to death due to wide macrophage activation, endothelial damage, and coagulation in critically ill patients. SARS‐CoV‐2‐induced lung injury due to inflammatory mediated thrombosis could be similar to the livedoid vasculopathy in the skin, supporting a translational comparison of these clinical settings. In this article, we discuss anticoagulation, suppression of inflammatory response, and hyperbaric oxygen therapy in the context of severe COVID‐19 and livedoid vasculopathy.     

Contributions of dermatologists to COVID‐19 research: A brief systematic review

Coronavirus disease 2019 (COVID‐19) has been declared a pandemic. We conducted a systematic review to reveal the contribution of dermatologists in COVID‐19 research. Two hundred and ninety‐eight articles were included and classified into cutaneous manifestations of COVID‐19, operating experience against COVID‐19, mechanisms and treatment of COVID‐19, disinfection and personal protective equipment (PPE)‐related skin diseases, and other topics. The value of these articles and their impact on clinical impact were discussed and we hope that dermatologists can have a better understanding of these areas from this study.     

COVID‐19 and immunological regulations – from basic and translational aspects to clinical implications

The COVID‐19 pandemic caused by SARS‐CoV‐2 has far‐reaching direct and indirect medical consequences. These include both the course and treatment of diseases. It is becoming increasingly clear that infections with SARS‐CoV‐2 can cause considerable immunological alterations, which particularly also affect pathogenetically and/or therapeutically relevant factors. Against this background we summarize here the current state of knowledge on the interaction of SARS‐CoV‐2/COVID‐19 with mediators of the acute phase of inflammation (TNF, IL‐1, IL‐6), type 1 and type 17 immune responses (IL‐12, IL‐23, IL‐17, IL‐36), type 2 immune reactions (IL‐4, IL‐13, IL‐5, IL‐31, IgE), B‐cell immunity, checkpoint regulators (PD‐1, PD‐L1, CTLA4), and orally druggable signaling pathways (JAK, PDE4, calcineurin). In addition, we discuss in this context non‐specific immune modulation by glucocorticosteroids, methotrexate, antimalarial drugs, azathioprine, dapsone, mycophenolate mofetil and fumaric acid esters, as well as neutrophil granulocyte‐mediated innate immune mechanisms. From these recent findings we derive possible implications for the therapeutic modulation of said immunological mechanisms in connection with SARS‐CoV‐2/COVID‐19. Although, of course, the greatest care should be taken with patients with immunologically mediated diseases or immunomodulating therapies, it appears that many treatments can also be carried out during the COVID‐19 pandemic; some even appear to alleviate COVID‐19.     

Management of urticaria in COVID‐19 patients: A systematic review

The global pandemic COVID‐19 has resulted in significant global morbidity, mortality and increased healthcare demands. There is now emerging evidence of patients experiencing urticaria. We sought to systematically review current evidence, critique the literature, and present our findings. Allowing PRISMA guidelines, a comprehensive literature search was carried out with Medline, EMBASE, Scopus, Cochrane, and Google Scholar, using key MeSH words, which include “COVID‐19,” “Coronavirus,” “SARS‐Cov‐2,” “Urticaria,” “Angioedema,” and “Skin rash” up to 01 August 2020. The key inclusion criteria were articles that reported on urticaria and/or angioedema due to COVID‐19 infection and reported management and outcome. Studies were excluded if no case or cohort outcomes were observed. Our search returned 169 articles, 25 of which met inclusion criteria. All studies were case reports, reporting 26 patients with urticaria and/or angioedema, COVID‐19 infection and their management and/or response. ajority of patients (n = 16, 69%) were over 50 years old. However, urticaria in the younger ages was not uncommon, with reported case of 2 months old infant. Skin lesions resolved from less than 24 hours to up to 2 weeks following treatment with antihistamines and/or steroids. There have been no cases of recurrent urticaria or cases nonresponsive to steroids. Management of urticarial in COVID‐19 patients should involve antihistamines. Low dose prednisolone should be considered on an individualized basis. Further research is required in understanding urticarial pathogenesis in COVID‐19. This will aid early diagnostic assessment in patients with high index of suspicion and subsequent management in the acute phase.     

Herpes zoster might be an indicator for latent COVID 19 infection

Various cutaneous manifestations have been observed in patients with COVID‐19 infection. Herpes zoster is a viral skin disease caused by varicella zoster that remains dormant in the dorsal root ganglia of cutaneous nerves following a primary chicken pox infection. In this report, we describe two cases COVID infection who first presented with herpes zoster. We are here by suggesting that the clinical presentation of HZ at the time of the current pandemic even in patients giving mild or no suggestive history of upper respiratory symptoms should be considered as an alarming sign for a recent subclinical SARS CoV2 infection.     

COVID‐19 knowledge prevents biologics discontinuation: Data from an Italian multicenter survey during RED‐ZONE declaration

SARS‐CoV‐2 become pandemics and there is still a dearth of data about its the potentially among dermatological patients under biologics. We aimed to assess health literacy, disease knowledge, treatment dissatisfaction and biologics attitudes toward COVID‐19. We performed a cross‐sectional, questionnaire‐based survey on 98/105 consecutive dermatological patients treated with biologics—51 suffering from plaque psoriasis, 22 from atopic dermatitis, and 25 from hidradenitis suppurativa. An ad hoc, validated questionnaire has 44 items investigating the following domains: knowledge of COVID‐19 related to (a) epidemiology, (b) pathogenesis, (c) clinical symptoms, (d) preventive measures, and (e) attitudes. Patients data and questionnaires were collected. Despite only 8.1% thought that biologics may increase the risk of COVID‐19, 18.4% and 21.4% of the patients were evaluating the possibility to discontinue or modify the dosage of the current biologic therapy, respectively. Globally, male patients (P = .001) with higher scholarity level (P = .005) displayed higher knowledge of COVID‐19. Patients with lower DLQI (P = .006), longer disease duration (P = .051) and lower scholarity (P = .007) have thought to discontinue/modify autonomously their biologic therapy. At the multivariate logistic regression, only the knowledge of epidemiology and preventive measures resulted independent predictors of continuation vs discontinuation and modification vs no modification, respectively. Dermatologists should promote COVID‐19 knowledge to prevent biologics disruption.     

COVID‐19 and implications for dermatological and allergological diseases

COVID‐19, caused by the coronavirus SARS‐CoV‐2, has become pandemic. A further level of complexity opens up as soon as we look at diseases whose pathogenesis and therapy involve different immunological signaling pathways, which are potentially affected by COVID‐19. Medical treatments must often be reassessed and questioned in connection with this infection. This article summarizes the current knowledge of COVID‐19 in the light of major dermatological and allergological diseases. It identifies medical areas lacking sufficient data and draws conclusions for the management of our patients during the pandemic. We focus on common chronic inflammatory skin diseases with complex immunological pathogenesis: psoriasis, eczema including atopic dermatitis, type I allergies, autoimmune blistering and inflammatory connective tissue diseases, vasculitis, and skin cancers. Since several other inflammatory skin diseases display related or comparable immunological reactions, clustering of the various inflammatory dermatoses into different disease patterns may help with therapeutic decisions. Thus, following these patterns of skin inflammation, our review may supply treatment recommendations and thoughtful considerations for disease management even beyond the most frequent diseases discussed here.     

COVID‐19 from the perspective of dentists: A case report and brief review of more than 170 cases

A novel coronavirus which has appeared from China, has been circulating hastily around the world. We summarized the publications including oral manifestation of coronavirus disease 2019 (COVID‐19) cases based on PubMed and Google Scholar data bases, and also present a case that highlights oral lesions 2 days prior to the first COVID‐19 general symptoms. Two authors independently reviewed the papers, 17 studies of more than 170 confirmed cases between ages of 9 and 90 were included. The most common oral manifestation was dry mouth followed by dysgeusia and pseudomembranous fungal structure. Change in tongue sensation and ulceration, muscle pain during mastication, swelling in oral cavity, and herpetic lesions were other common symptoms. Associated symptoms, latency time, treatment, and prognosis have also been meticulously reviewed. We hope that careful clinical intraoral examination on all COVID‐19 positive patients and equally on any patients who need dental care will pave the way for further studies.     

Treatment considerations for Behçet disease in the era of COVID‐19: A narrative review

COVID‐19 is a multisystem disease caused by severe acute respiratory syndrome coronavirus 2. It has been declared a pandemic by the World Health Organization in March 2020 and the outbreak still keeps its impacts worldwide. Behçet disease (BD) is a multi‐systemic vasculitis involving the skin, mucosa, eyes, joints, nervous system, cardiovascular system, and gastrointestinal system. The precise etiopathogenesis of the disorder is unknown but autoimmunity is believed to play a key role. A considerable part of patients with BD are susceptible to immunosuppression and are more predisposed to infections than healthy individuals. Hence, the protection and control measures for patients with BD against the COVID‐19 are of the utmost significance. Given the requirement to balance proper treatment of BD with the smallest risk of COVID‐19 associated mortality and morbidity, we aimed to review the management of BD in the era of the pandemic with a special focus on treatment considerations. According to current expert recommendations, there is no reason to discontinue topical treatments, colchicine, and nonsteroidal antiinflammatory drugs. Systemic steroids can be used at the lowest possible dose if needed. Ongoing treatments can be continued unchanged in patients with no suspected or confirmed COVID‐19. In cases with COVID‐19 symptoms, immunosuppressive and biological agents can be temporarily stopped but the decision should be made on a case by case basis. Considering their potential beneficial effects on the course of COVID‐19, colchicine, pentoxifylline, and dapsone can be considered as safe treatment options in BD.