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      Erythema annulare centrifugum triggered by SARS‐CoV‐2 infection

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          Abstract

          Erythema annulare centrifugum (EAC) is a reactive phenomenon of the skin that has been reported to occur in association with numerous conditions, including infections. 1 It commonly presents with annular, erythematous plaques with a fine desquamation in the inner portion of the advancing edge. 2 In the last year, a wide spectrum of cutaneous manifestations has been associated with SARS‐CoV‐2 infection, including acral areas of erythema with vesicles or pustules, other vesicular eruptions, urticarial lesions, maculopapular eruptions and livedo or necrosis. 3 , 4 A 37‐year‐old otherwise healthy woman presented with a 1‐week history of itching skin lesions on the arms and back. She referred history of fever, headache and malaise 2 weeks before the onset of these lesions. A nasopharyngeal reverse transcription‐polymerase chain reaction (RT‐PCR) was positive for SARS‐CoV‐2 at that time. Physical examination revealed multiple erythematous papules and annular plaques with central clearing and a delicate scale on the inner margin on the upper arms and back (Fig. 1). Potassium hydroxide test was negative. Histopathology showed a prominent perivascular lymphocytic infiltrate on papillary dermis and occasionally on reticular dermis, with endothelial tumefaction, hematic extravasation and sparse interstitial eosinophils (Fig. 2). Clinicopathologic findings were compatible with EAC. A routine laboratory work‐up had no alterations. Treatment with clobetasol propionate 0.05% cream was applied once daily for 2 weeks with completely resolution of the lesions. Figure 1 Multiple erythematous papules and annular plaques with a trailing scale on the upper arms. Figure 2 Prominent perivascular lymphocytic infiltrate on papillary dermis in a ‘coat sleeve’ appearance with endothelial tumefaction, hematic extravasation and sparse interstitial eosinophils. EAC is a gyrate erythema characterized by erythematous papules that expand centrifugally with central clearing resulting in annular plaques. 2 Typically, a fine scale is present in the inner portion of the advancing edge, known as trailing scale. 2 Pruritus is variable, and the most frequent localizations are the trunk and lower extremities. 1 EAC is thought to be a delayed‐type hypersensivity response to a wide variety of antigens. Possible triggers may include viral, bacterial or fungal infections, medications, foods, malignancy or other systemic diseases. 1 , 2 , 5 However, in many patients, a specific trigger cannot be recognized. 6 Histopathologic findings in EAC consist of a dense perivascular lymphocytic infiltrate on papillary dermis and possibly reticular dermis, which is known as a ‘coat sleeve’ appearance. Variable oedema, spongiosis, parakeratosis and basal layer vacuolization may be present. 1 Differential diagnosis includes other skin disorders that may present with annular, erythematous lesions such as erythema migrans, tinea, pityriasis rosea, psoriasis, granuloma annulare and annular lupus erythematosus. 1 , 7 In our case, the typical clinic and histopathologic findings of EAC together with SARS‐CoV‐2 infection confirmed by a RT‐PCR 2 weeks before supported the theory of a possible association. EAC has been suggested to be a tumour necrosis alpha (TNF‐alpha) dependent process. 8 Therefore, the proinflammatory cytokines released during SARS‐CoV‐2 infection could be involved in the pathogenesis of EAC. 7 To our knowledge, there is only one previous report of EAC presumptive triggered by SARS‐CoV‐2. The patient presented with clinical and histopathological skin lesions consistent with EAC accompanied by anosmia and ageusia that completely resolved with doxycycline. 7 However, a RT‐PCR was not obtained at that time and diagnosis of SARS‐CoV‐2 was made two months later based on a serological screening test. 7 Usually, EAC has a self‐limited course and good prognosis. 2 Data on treatment for EAC are sparse. Topical corticosteroids, topical vitamin D analogues, metronidazole, macrolides (azithromycin, erythromycin), fluconazole and etanercept have been reported to be useful in some cases. 2 , 7 , 8 We report the second case of EAC probably triggered by SARS‐CoV‐2 in a patient with confirmed infection by nasopharyngeal RT‐PCT 2 weeks before the onset of the cutaneous lesions that completely resolved with clobetasol propionate 0.05% cream. Conflict of interest All the authors declare no conflict of interest. Funding sources There are no founding sources.

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          Classification of the cutaneous manifestations of COVID‐19: a rapid prospective nationwide consensus study in Spain with 375 cases

          Summary Background Cutaneous manifestations of COVID‐19 disease are poorly characterized. Objectives To describe the cutaneous manifestations of COVID‐19 disease and to relate them to other clinical findings Methods Nationwide case collection survey of images and clinical data. Using a consensus, we described 5 clinical patterns. We later described the association of these patterns with patient demographics, timing in relation to symptoms of the disease, severity, and prognosis. Results Lesions may be classified as acral areas of erythema with vesicles or pustules (Pseudo‐chilblain) (19%), other vesicular eruptions (9%), urticarial lesions (19%), maculopapular eruptions (47%) and livedo or necrosis (6%). Vesicular eruptions appear early in the course of the disease (15% before other symptoms). The pseudo‐chilblain pattern frequently appears late in the evolution of the COVID‐19 disease (59% after other symptoms), while the rest tend to appear with other symptoms of COVID‐19. Severity of COVID‐19 shows a gradient from less severe disease in acral lesions to most severe in the latter groups. Results are similar for confirmed and suspected cases, both in terms of clinical and epidemiological findings. Alternative diagnoses are discussed but seem unlikely for the most specific patterns (pseudo‐chilblain and vesicular). Conclusions We provide a description of the cutaneous manifestations associated with COVID‐19 infection. These may help clinicians approach patients with the disease and recognize paucisymptomatic cases.
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            COVID‐19 and cutaneous manifestations: A systematic review

            Abstract The cutaneous manifestations of COVID‐19 patients have been increasingly reported, but not summarized, and the potential mechanisms remain to be investigated. Herein, we performed a comprehensive review of literatures (from inception to May 30, 2020) using PubMed, CNKI, medRxiv, and bioRxiv with the terms “((novel coronavirus) OR (2019 novel coronavirus) OR (2019‐nCoV) OR (Coronavirus disease 2019) OR (COVID‐19) OR (SARS‐CoV‐2)) AND ((Dermatology) OR (skin) OR (rash) OR (cutaneous))” and “((ACE2) OR (Angiotensin‐converting enzyme)) AND ((skin) OR (epidermis) OR (dermis))”. Totally, 44 articles met the inclusion criteria. A total of 507 patients with cutaneous manifestations were summarized, and 96.25% patients were from Europe. The average age of the patients was 49.03 (range: 5‐91) with a female ratio of 60.44%. The skin lesions were polymorphic, and erythema, chilblain‐like and urticarial lesions were most common, occurring on an average of 9.92 days (range: 1‐30) after the onset of systemic symptoms. The receptor of SARS‐CoV‐2, ACE2, was found to be expressed on skin, mainly on keratinocytes. Our review systematically presented the clinical characteristics of 507 patients and showed that skin might be the potential target of the infection according to ACE2 expression. More work should be done to better understand the underlying pathogenesis.
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              Is Open Access

              Erythema Annulare Centrifugum: Analysis of Associated Diseases and Clinical Outcomes according to Histopathologic Classification

              Dear Editor: Erythema annulare centrifugum (EAC), a chronic inflammatory skin disease with an unknown etiology, is considered a hypersensitivity reaction caused by cutaneous or systemic infection, malignant neoplasms, drugs, and various autoimmune diseases, among other factors1 2. Clinically, EAC presents as erythematous papules or plaques that enlarge by peripheral extension with central clearing, resulting in an annular or polycyclic appearance1 3. Kim et al.3 previously reported that EAC is associated with various underlying conditions, including infectious and immunologic diseases, consumption of certain food, and drug use. Furthermore, Weyers et al.4 suggested that, although EAC is generally classifiedas either superficial or deep, the term should be reserved for the superficial type only, as these types appear to be separate clinicopathologic entities, and the deep type should hence be classified as another disease entity. Meanwhile, Ziemer et al.5 concluded that EAC is a clinical reaction pattern rather than a specific clinicopathologic entity. As mentioned above, histopathologically, based on the extent of perivascular lymphocytic infiltration, EAC can be divided into superficial and deep types. However, according to this histopathologic classification, the clinical characteristics are currently not fully understood. Thus, the purpose of this study was to analyze the clinical features, associated diseases, recurrence rates, and treatment outcomes of EAC according to the histopathologic subtypes. We retrospectively analyzed the medical records and biopsy specimens of 39 patients histopathologically diagnosed with EAC at the Department of Dermatology at the Catholic Medical Center (Seoul, Korea) between January 2003 and December 2013. The Institutional Review Board of the Catholic Medical Center granted approval (XC14RIMI0086) for the review of the medical records, and the study protocol was conducted in accordance with the Helsinki Declaration of 1975 (as revised in 2000). Associated diseases were confined to cases that occurred before the development of EAC and that showed a correlation with the clinical course of EAC. We divided the treatment outcomes into three groups: (1) excellent (>50% improvement in the skin lesion within 3 months after treatment), (2) moderate (took more than 3 months to achieve >50% improvement after treatment), and (3) poor (<50% improvement at 3 months after treatment)6. Recurrence was defined as skin lesions showing aggravation after an excellent response. We reviewed the histopathologic slides of the patients, and classified the cases that presented with various epidermal changes (hyperkeratosis, parakeratosis, spongiosis, or basal vacuolar degeneration) and perivascular lymphocyte infiltration in the upper dermis into superficial EAC. In contrast, cases that showed no or minimal epidermal changes, mild edema in the papillary dermis, and perivascular inflammatory cells (lymphocyte predominant) in the upper and deep dermis were classified as the deep type. Data analysis was conducted using IBM SPSS Statistics ver. 22.0 (IBM, Armonk, NY, USA). For categorical data, χ2 or Fisher's exact test was used as appropriate. A p-value<0.05 was considered statistically significant. Among the 39 patients, 13 patients (33.3%) showed associated conditions, including cutaneous fungal infection (n=5), pregnancy (n=2), malignancy (thyroid cancer, n=2), autoimmune diseases such as Behcet disease and rheumatoid arthritis (n=2), and medication use (cephalosporin, n=2). Based on the histopathologic findings, 32 cases (82.1%) were classified into the superficial type, and 7 cases (17.9%) into the deep type (Table 1). Twenty-seven (superficial type, n=22; deep type, n=5) of the 39 patients had available follow-up data from our clinic after the skin biopsy, and their clinical outcomes were as follows: 5 patients (18.5%) showed persistent skin lesions without improvement (poor response) over 1 year. The average duration of continuous skin lesionswas 4.7 months. Thirteen (48.1%), 7 (25.9%), and 7 patients (25.9%) showed the excellent, moderate, and poor responses, respectively. Of the 7 cases with a poor response, 1 and 6 cases were deep and superficial EAC, respectively. Eleven of the 32 superficial cases (34.4%) were associated with another disease, whereas 2 out of the seven deep cases (28.6%) had associated diseases. These results indicated that there were no remarkable differences in the incidence rates of associated diseases between the superficial and deep types of EAC (p=1) (Table 1). However, a distinct difference between the superficial and deep types was observed for the average duration of continuous skin lesions (4.1 vs. 8.1 months). The recurrence rate was 31.8% for the superficial type, whereas no deep EACs showed recurrence. In terms of treatment outcomes, 27.3% and 20.0% of patients with the superficial and deep types respectively revealed a poor response to treatment; there was little difference between these two types (p=0.965) (Table 2). There were some limitations to this study, including the fact that it was a retrospective study and that the number of deep-type cases was small. Accordingly, further large-scale prospective studiesare required to ascertain these results. In conclusion, our findings revealed differences in the clinical outcomes according to the histopathologic subtype of EAC, with the superficial type being associated with a higher recurrence rate and a shorter duration of skin lesions compared with the deep type.
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                Author and article information

                Contributors
                nurisetorrent@gmail.com
                Journal
                J Eur Acad Dermatol Venereol
                J Eur Acad Dermatol Venereol
                10.1111/(ISSN)1468-3083
                JDV
                Journal of the European Academy of Dermatology and Venereology
                John Wiley and Sons Inc. (Hoboken )
                0926-9959
                1468-3083
                15 September 2021
                15 September 2021
                : 10.1111/jdv.17645
                Affiliations
                [ 1 ] Department of Dermatology Hospital Universitari Sagrat Cor – Grupo Hospitalario Quirónsalud Barcelona Spain
                [ 2 ] Department of Pathology Hospital Universitari General de Catalunya – Grupo Hospitalario Quirónsalud Barcelona Spain
                Author notes
                [*] [* ] *Correspondence: N. Setó‐Torrent. E-mail: nurisetorrent@ 123456gmail.com

                Author information
                https://orcid.org/0000-0001-7922-9905
                https://orcid.org/0000-0003-3916-9105
                https://orcid.org/0000-0002-2366-7110
                Article
                JDV17645
                10.1111/jdv.17645
                8657360
                34487601
                eaeb7d44-ae5e-4a90-810b-843d47d15c79
                © 2021 European Academy of Dermatology and Venereology

                This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

                History
                : 10 July 2021
                : 26 August 2021
                Page count
                Figures: 2, Tables: 0, Pages: 2, Words: 2004
                Categories
                Letter to the Editor
                Letters To The Editor
                Custom metadata
                2.0
                corrected-proof
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.9 mode:remove_FC converted:09.12.2021

                Dermatology
                Dermatology

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