key: cord-0711376-sraqdkri authors: Farajzadeh, Saeedeh; Khalili, Maryam; Dehghani, Shakiba; Babaie, Sharareh; Fattah, Mahdi; Abtahi‐Naeini, Bahareh title: Top 10 acral skin manifestations associated with COVID‐19: A scoping review date: 2021-10-21 journal: Dermatol Ther DOI: 10.1111/dth.15157 sha: 2d620cac60c5c6535d0cbf49be54f98f86ef4e29 doc_id: 711376 cord_uid: sraqdkri COVID‐19‐associated cutaneous manifestations are one of the most important and relatively common extra‐respiratory presentations of SARS‐COV‐2 infection. The exact identification and classification of these lesions can facilitate the accurate diagnosis and treatment. There are several case reports and small case series which describe cutaneous lesions in hands and feet. Currently, there is no scoping review about acral skin manifestations associated with COVID‐19. This paper covers the COVID‐related acral skin manifestations in 10 entities including acral papulo‐vesicular eruption, acral urticarial lesion, acral non‐inflammatory purpura and necrosis, acro‐ischemia associated COVID‐19, acral vasculitis, chilblain‐like lesion (COVID Toe), acral erythema multiform (EM) like lesion, hand and foot skin lesions associated with multisystem inflammatory syndrome in children (MISC), acral peeling conditions and red half‐moon nail sign. Future studies should focus on exact investigation of etiologies of these lesions including role of immune senescence, environment, gender, immunogenetics and relation of these lesion with major organ involvements. Occasionally, acral skin lesions may represent the initial presentation of SARS-CoV-2 infection prior to fever or respiratory manifestations. Moreover, several acral cutaneous manifestations could be associated with poor prognosis or additional medical conditions. 5 Thus, recognition of covid-19 related acral signs and symptoms can help clinicians to consider COVID-19 in the differential diagnoses of acral skin lesions. Some of the most common acral skin presentations of COVID-19 include: acral papulo-vesicular eruption, acral urticarial lesion, acral non-inflammatory purpura and necrosis, acro-ischemia associated COVID-19, acral vasculitis, chilblain-like lesion (COVID Toe), acral erythema multiform (EM) like lesion, hand and foot skin lesions associated with multisystem inflammatory syndrome in children (MISC), acral peeling conditions and red half-moon nail sign. As explained above, we conducted a scoping review to summarize the different acral skin lesions associated with COVID-19 in children and adults as to recognize distinct cutaneous signs in COVID-19 patients for accurate use of each entity and to prevent confusion among clinicians in similar entities. We also provided a table to categorize these findings more (Table 1) (Figure 1 ). The possible explanation for development of acral papulo-vesicular lesions is immune system hyperactivity and direct cytopathic effect of SARS-CoV-2 on endothelial dermal vessels. 9 Histological features include prominent acantholysis and dyskeratosis associated with intraepidermal vesicles in supra-basal location. In some cases, epidermal necrosis, swelling of keratinocytes, ballooning degeneration of keratinocytes and endotheliitis may be present. 10,11 There is no standard treatment for COVID-19-associated papulovesicular lesions. A "watchful waiting" strategy and symptomatic therapy is recommended. 12 Urticarial lesions typically present as an erythematous papule or plaque with or without angioedema and intense pruritus. Among the most common sites of involvement are extremities including acral sites. 13, 14 (Figure 2 ). Possible explanations for urticaria associated with COVID-19 are direct cutaneous effect by SARS-CoV-2 virus, drug-induced exanthema and over activity of the immune system. 13 Pathological findings of urticarial lesions in COVID-19 patients consist of superficial perivascular infiltration of lymphocytes with few eosinophilic infiltrations associated with marked dermal edema in upper dermis. 6 Urticarial lesions are usually associated with moderate to severe COVID-19. Non-sedating antihistamines can be used for treatment of COVID-19-associated urticarial lesions. In more severe cases, a short course of low-dose systemic corticosteroids can be used. 13 2.3 | Acral non-inflammatory purpura and skin necrosis Most cases of purpura associated with COVID-19 are noninflammatory retiform purpura presented as a lace-like reddish-blue to purple mottled discolorations on extremities and acral sites. These purpuric lesions may evolve into hemorrhagic blisters or necroticulcerative lesions and dry gangrene. 15, 16 (Figure 3 ). Hypercoagulative state associated with COVID-19 and pauciinflammatory micro thrombotic vasculopathy are proposed as the underlying mechanisms for purpuric lesions. 12 In addition, the cutaneous side effects of anti-COVID-19 agents like high-dose intravenous immunoglobulin (IVIG) should be considered as skin manifestations of microvascular occlusion syndrome. 17 Pauci-inflammatory thrombogenic vasculopathy with extensive deposition of complement components within the cutaneous microvasculature are dominant histopathological features of non-inflammatory petechial and purpural lesions. 18 Petechia, purpura and acral necrotic lesions are usually associated with greater severity of COVID-19. 18 Since acral non-inflammatory purpura and skin necrosis are cutaneous signs of thrombotic microangiopathy, therapeutic-dose of anticoagulants is appropriate for documented evidence of thrombosis or ongoing thrombosis formation. 19 T A B L E 1 Summary of clinical manifestations, ethiopathogenesis, histopathological findings and clinical management of 10 acral skin manifestations in COVID-19 No. conditions. 29 ( Figure 6 ). Chilblain Figure 9 ). The exact mechanism of acral peeling lesions in association with COVID-19 is unclear. Similar to other post infections with significant inflammatory response, alternation in regulation of expression of acral keratins can be considered as possible mechanism. 46 Due to mild and self-limiting nature of these lesions, skin biopsy is usually not performed. Treatment is usually not necessary as lesions spontaneously resolve within 1-4 weeks. 46 2.10 | Red half-moon nail sign associated with COVID-19 Half-moon-shaped transversal red band at the distal margin of the lunula as single crescent erythronychia on the nail bed is considered as a pathognomonic nail finding in COVID-19 infection. 47 The authors declare that none of the authors are employed by a government agency that has a primary function other than research and/or education. None of the authors is an official representative or on behalf of the government. Besides, the authors declare that written informed consents were obtained from the patients or their guardians for publication of this review and any accompanying images. The authors declare no conflict of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request. https://orcid.org/0000-0003-1866-7092 Shakiba Dehghani https://orcid.org/0000-0002-6508-778X Skin manifestations of COVID-19: A worldwide review Cutaneous and histopathological features of coronavirus disease 2019 in pediatrics: A review article Atlas of Dermatology, Dermatopathology and Venereology Cutaneous manifestations in confirmed COVID-19 patients: a systematic review Management of a child vs an adult presenting with acral lesions during the COVID-19 pandemic: a practical review Clinical and histological characterization of vesicular COVID-19 rashes: a prospective study in a tertiary care hospital Varicella-like exanthem as a specific COVID-19-associated skin manifestation: multicenter case series of 22 patients Cutaneous manifestations in COVID-19: a first perspective Are the cutaneous manifestations during or due to SARS-CoV-2 infection/COVID-19 frequent or not? Revision of possible pathophysiologic mechanisms Histology of skin lesions establishes that the vesicular rash associated with COVID-19 is not 'varicella-like Clinicopathologic aspects of a papulovesicular eruption in a patient with COVID-19 Skin manifestations associated with COVID-19: current knowledge and future perspectives Classification of the cutaneous manifestations of COVID-19: a rapid prospective nationwide consensus study in Spain with 375 cases Chilblains is a common cutaneous finding during the COVID-19 pandemic: a retrospective nationwide study from France Retiform purpura as a dermatological sign of coronavirus disease 2019 (COVID-19) coagulopathy Vascular skin symptoms in COVID-19: a French observational study The broad spectrum of dermatological manifestations in COVID-19: clinical and histopathological features learned from a series of 34 cases Cutaneous manifestations related to coronavirus disease 2019 (COVID-19): a prospective study from China and Italy American Society of Hematology 2021 guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19 Acute acro-ischemia in the child at the time of COVID-19 Chilblain and acral purpuric lesions in Spain during Covid confinement: retrospective analysis of 12 cases Acro-ischemic lesions associated with extremely elevated D-dimer in a child during the COVID-19 pandemic Systemic thrombolysis as initial treatment of COVID-19 associated acute Aortoiliac and lower extremity arterial thrombosis When interferon tiptoes through COVID-19: Pernio-like lesions and their prognostic implications during SARS-CoV-2 infection Cutaneous small vessel vasculitis secondary to COVID-19 infection: a case report Leucocytoclastic vasculitis: an update for the clinician A unilateral purpuric rash in a patient with COVID-19 infection COVID-19 in children: the link in the transmission chain COVID toes: where do we stand with the current evidence? A chilblain epidemic during the COVID-19 pandemic. A sign of natural resistance to SARS-CoV-2? Med Hypotheses New insights in COVID-19-associated chilblains: a comparative study with chilblain lupus erythematosus Acral rash in a child with COVID-19 Approach to chilblains during the COVID-19 pandemic Erythema multiforme-like lesions in children and COVID-19 Synthesis of the data on COVID-19 skin manifestations: underlying mechanisms and potential outcomes Dermatological manifestation of pediatrics multisystem inflammatory syndrome associated with COVID-19 in a 3-year-old girl The natural history of severe acute respiratory syndrome coronavirus 2-related multisystem inflammatory syndrome in children: a systematic review Multi-system inflammatory syndrome in children (MIS-C) following SARS-CoV-2 infection: review of clinical presentation, hypothetical pathogenesis, and proposed management Histologic and Immunohistochemical evaluation of infiltrating inflammatory cells in Kawasaki disease arteritis lesions Cutaneous Clinico-pathological findings in three COVID-19-positive patients observed in the metropolitan area of Clinical and histopathological study of skin dermatoses in patients affected by COVID-19 infection in the northern part of Italy Multisystem inflammatory syndrome in children: a systematic review Giant Urticaria and Acral peeling in a child with coronavirus disease 2019 Mucocutaneous manifestations of multisystem inflammatory syndrome in children during the COVID-19 pandemic Mucocutaneous disease and related clinical characteristics in hospitalized children and adolescents with COVID-19 and multisystem inflammatory syndrome in children Acral peeling as the sole skin manifestation of COVID-19 in children The red half-moon nail sign: a novel manifestation of coronavirus infection COVID-19 and nail manifestation: be on the lookout for the red half-moon nail sign Top 10 acral skin manifestations associated with COVID-19: A scoping review