key: cord-1002682-xrkaasqb authors: Shams, Saad; Rathore, Sawai Singh; Anvekar, Priyanka; Sondhi, Manush; Kancherla, Neeraj; Tousif, Sohaib; Rojas, Gianpier Alonzo; Ahmed, Noman Khurshid; Munawwar, Mehwish; Noman, Muhammad title: Maculopapular skin eruptions associated with Covid‐19: A systematic review date: 2021-02-02 journal: Dermatol Ther DOI: 10.1111/dth.14788 sha: e2e2d2b487637388d3f83d1d366c139ec54888a9 doc_id: 1002682 cord_uid: xrkaasqb In this systematic review, we anticipated in summarizing clinical features, histopathological hallmarks, and possible pathology behind the maculopapular skin eruptions occurring in Covid‐19 patients. A literature search was executed using MEDLINE/PubMed and Embase databases for articles published till 20 November 2020. All eligible articles including observational studies, case reports, and case series reporting the maculopapular skin lesion in Covid‐19 patients were included. Data were obtained for 354 Covid‐19 patients presenting with maculopapular lesions from 40 studies. The mean age of these patients was 53 years, and with 42% of them being male. These maculopapular lesions differed considerably in terms of distribution and appearance, ranging from diffuse erythematous maculopapular lesions to scattered erythematous macules coalescing into papules to maculopapular lesions in plaques. The mean duration of the lesion was 8 days. These lesions were frequently localized on trunks and extremities. Superficial perivascular dermatitis with lymphocytic infiltrate was a histopathological hallmark of these lesions. As these skin lesions may have a possible association with diagnosis, management, prognosis, and severity of the disease, all health practitioners need to be well acquainted with these Covid‐19 skin lesions. Also, in the middle of this worldwide pandemic, early identification of this eruption may help manage this infection's further spread. A new infectious pathogen called severe acute respiratory syndrome (SARS-CoV-2) came into view in Wuhan, China, in December 2019 1 . It was associated with an unconventional cause of pneumonia. The disease was later entitled Coronavirus disease 2019 . Following then it has quickly disseminated across the globe. Due to its asymptomatic transmission, high infectivity rate, and high mortality rate among the elderly and immunocompromised, it was declared a pandemic by the world health organization on March 11. By through end of November, 63 million cases of Covid-19 have been documented worldwide, accompanied by 1.34 million deaths. 2 SARS-CoV-2 is a β-Coronavirus, which is an enveloped, positivesense, single-stranded RNA virus. 3 SARS-CoV-2 enters the human cell via protein receptor angiotensin-converting enzyme 2 (ACE2) and causes infection. Despite the fact that this virus predominantly targets the respiratory tract, several human tissues, including gastrointestinal and skin tissue have been discovered to have ACE2 expression, this may contribute to dermatologic finding present in Covid- 19. 4 The clinical manifestation of Covid-19 is pretty diverse, extending from mild symptoms to critical lethal respiratory failure, septic shock, ultimately to multiorgan failure. The most common clinical symptoms of SARS-CoV-2 infection include fever, dry cough, fatigue, sore throat, and dyspnea, and headache; less commonly, vomiting, diarrhea, and anosmia or ageusia. 1 Besides these typical symptoms, new symptoms including a range of cutaneous manifestations have been recorded globally. The first record of cutaneous signs was documented in a study from China, in this study out of 1099 Covid-19 patients only, 2 (0.2%) presented with cutaneous manifestation. 5 Later another report from Italy reported a higher prevalence of about 21% of the patient out of 88 presenting with cutaneous manifestation. 6 Subsequently, many case reports and case series have been published reporting this manifestation in Covid-19 patients. These cutaneous lesions vary greatly in terms of clinical features of which maculopapular eruptions seem to be one of the most common lesions occurring in about 22% to 47% of Covid-19 cases presenting with cutaneous manifestation. [7] [8] [9] As these lesions may provide a sooner and more reliable diagnosis and management of the infection, It is important for all health practitioners to be well acquainted with these Covid-19 skin lesions. Also, in the middle of this worldwide pandemic, early identification of this eruption may also help in managing the further spread of this infection. In this systematic review, we aim to summarize clinical features, histopathological hallmarks, and possible pathology behind the maculopapular skin lesion occurring in Covid-19 patients. The existing systematic review is accomplished and reported in conjunction with preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. 10 All eligible articles including observational studies, case reports, and case series reporting the maculopapular skin lesion in Covid-19 patients were included. Articles like review articles, hypothesis articles, and commentaries were discarded. The title and abstract of studies from formerly investigated databases were evaluated by three authors (S. T., N. K.). These authors ascertained studies, on the basis of predetermined eligibility criteria. From these selected studies, three authors (S. S. R., P. A., M. S.) retrieved data manually. For every report, subsequent details were extracted, author, country of origin, study design, sample size, mean age, clinical features of skin lesions, mean duration, location of skin lesion, sign, and symptoms, laboratory findings, histopathological findings, treatment of Covid-19, and outcome of the lesion. Zika, and HIV are common viral infections associated with maculopapular rash. 12 The maculopapular eruption is prominent on the chest, back, abdomen, and extremities and can range from confluent lesions to erythematous, scattered blanching rash. Article stating the association of maculopapular rash with Covid-19 infection has diverse clinical depiction. Distribution and appearance of maculopapular eruption ranged from diffuse erythematous maculopapular lesions to scattered erythematous macules coalescing into papules to maculopapular lesions in plaques to erythematous macules and plaques with a violaceous targetoid appearance. Some maculopapular lesions associated with Covid-19 were marked by a petechial portion. [13] [14] [15] [16] Detailed clinical characteristics features of the lesion from each study are compiled in Table 2 . Many lesions presented with itching while in few cases manifested with a burning sensation. 9, 17 Two reports described the painful character of maculopapular lesion. 8, 18 Some reports have identified a substantial craniocaudal development of a rash, involving the folds without the engagement of the palmar-plantar area and the mucous membranes. 15 In most of the studies, lesions appeared either at onset or after the onset of other symptoms of Covid-19 however, few studies reported the appearance of rash 2 to 3 days before the onset of symptoms. 8, 9, 25, 26 One observational study suggested an increased severity of Covid-19 illness in patients with maculopapular lesions, which was established by a 2% mortality rate recorded in those patients. 8 The most frequent medication used in these patients with maculopapular lesions were hydroxychloroquine/chloroquine ( reported that 78% of maculopapular lesions had concurrent drug consumption. 36 The most common drug taken by these patients was chloroquine/hydroxychloroquine, followed by lopinavir/ritonavir, tocilizumab, and azithromycin. 36 A case report by Mazan et al described the development of Itchy, maculopapular rash with nontender erythematous macules and papules following 10 days of lopinavir/ritonavir administration. 37 In spite of this, in case series with the patients taking no new medications, the maculopapular rash has been recognized, hinting that these lesions may not just be associated with drugs. 38 As can be observed, Covid-19 related maculopapular rash can In this article, a systematic review of the cutaneous maculopapular eruptions associated with SARS-COV-2 is provided. Covid-19 patients most typically have respiratory symptoms, but multiple organ involvement with various cutaneous signs like maculopapular rash may occur. These maculopapular lesions differ considerably in terms of distribution and appearance, ranging from diffuse erythematous maculopapular lesions to scattered erythematous macules coalescing into papules to maculopapular lesions in plaques and may resemble other well-known dermatological disorders. Even though these results do not suggest that Covid-19 is the absolute cause of these maculopapular eruptions, they indicate these lesions should be regarded in the context of possible presentations associated with this illness. As these lesions may have a possible association with diagnosis, management, prognosis, and severity of the disease, all health practitioners need to be well acquainted with these Covid-19 skin lesions. Also, in the middle of this worldwide pandemic, early identification of this eruption may help manage this infection's further spread. 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A case series of seven patients A case of COVID-19 pneumonia in a young male with full body rash as a presenting symptom Morbilliform exanthem associated with COVID-19 Vascular skin symptoms in COVID-19: a French observational study Comment on "cutaneous manifestations in COVID-19: a first perspective" by Recalcati S Cutaneous manifestations in the current pandemic of coronavirus infection disease (COVID 2019) Cutaneous manifestations in COVID-19: a skin rash in a child SARS-CoV-2, skin lesions and the need of a multidisciplinary approach Histological pattern in COVID-19-induced viral rash Skin manifestations in patients hospitalized with confirmed COVID-19 disease: a cross-sectional study in a tertiary hospital Coronavirus disease 2019 (COVID-19) accompanied by maculopapular rash: a case study Isolated maculopapular eruption localized to head and neck: a cutaneous sign of COVID-19 infection Acute maculopapular eruption in Covid-19 patient: a case report Maculopapular rash in COVID-19 patient treated with lopinavir/ritonavir Development of maculopapular exanthem in a COVID-19 patient Cutaneous eruption in COVID-19-infected patients in Thailand: an observational descriptive study How to cite this article: Shams S, Rathore SS, Anvekar P, et al. Maculopapular skin eruptions associated with Covid-19: A systematic review The authors declare no potential conflict of interest. All authors contributed equally to this work. The data that support the findings of this study are available within the article, in the reference list. The data that support the findings of this study are available from thecorresponding author upon reasonable request. Sawai Singh Rathore https://orcid.org/0000-0003-1954-094XManush Sondhi https://orcid.org/0000-0002-3910-1189Gianpier Alonzo Rojas https://orcid.org/0000-0002-4937-0227