key: cord-0850455-t0gtwi7f authors: Gottlieb, Michael; Long, Brit title: Dermatologic manifestations and complications of COVID-19 date: 2020-06-06 journal: Am J Emerg Med DOI: 10.1016/j.ajem.2020.06.011 sha: 3727ca36326cf71ba404dd5014e1bbc371414569 doc_id: 850455 cord_uid: t0gtwi7f The novel coronavirus disease of 2019 (COVID-19) is associated with significant morbidity and mortality. While much of the focus has been on the cardiac and pulmonary complications, there are several important dermatologic components that clinicians must be aware of. OBJECTIVE: This brief report summarizes the dermatologic manifestations and complications associated with COVID-19 with an emphasis on Emergency Medicine clinicians. DISCUSSION: Dermatologic manifestations of COVID-19 are increasingly recognized within the literature. The primary etiologies include vasculitis versus direct viral involvement. There are several types of skin findings described in association with COVID-19. These include maculopapular rashes, urticaria, vesicles, petechiae, purpura, chilblains, livedo racemosa, and distal limb ischemia. While most of these dermatologic findings are self-resolving, they can help increase one's suspicion for COVID-19. CONCLUSION: It is important to be aware of the dermatologic manifestations and complications of COVID-19. Knowledge of the components is important to help identify potential COVID-19 patients and properly treat complications. J o u r n a l P r e -p r o o f were also included. The initial literature search revealed 1,553 articles. Authors reviewed all relevant articles and decided which studies to include for the brief report by consensus, with focus on emergency medicine-relevant articles. A total of 41 resources were selected for inclusion in this review. SARS-CoV-2 is an RNA virus that may enter cells through the angiotensin-converting enzyme 2 (ACE2) receptor found on lung alveolar epithelial cells, small intestine enterocytes, and vasculature, as well as neurologic, endocrine, and cardiac systems. [3, 4] ACE2 plays several key roles in normal physiology, including breakdown of angiotensin II. [4] SARS-CoV-2 may cause direct lung injury and systemic inflammation, as well as increased coagulation. [5] [6] [7] These factors can result in multiorgan dysfunction. Recent literature suggests ACE2 is also located in J o u r n a l P r e -p r o o f While the most common symptoms of COVID-19 include congestion, cough, dyspnea, and fever, skin symptoms can occur in up to 20.4% of patients. [9] One early study found that only 2 of 1,099 patients had a "rash", but investigators may have missed several patients. [2] A more recent study found rash occurred in 18 of 88 patients, with 8 of these patients having rash at onset, while another study found that rash occurred in 5 out of 103 patients. [9, 12] There are several proposed etiologies for rash in patients with COVID-19. The first is diffuse microvascular vasculitis, resulting from complement system activation. One study found significant complement protein deposition in the dermal capillaries, as well as interstitial and perivascular neutrophilia with prominent leukocytoclasia, suggesting a vasculitic phenomenon. [13] Others have suggested that this occurs as a direct effect of the virus. This has been based on high concentrations of lymphocytes without eosinophils, papillary dermal edema, epidermal spongiosis, and lymphohistiocytic infiltrates. [14, 15] A rash associated with COVID-19 can involve various body regions, most commonly the trunk, but extremity involvement may also occur. [9] Pruritus is often minimal but depends on the type of rash, and lesions typically heal quickly, appearing within 3 days and disappearing within 8 days. [9, 16] A challenging aspect of rash associated with COVID-19 is the myriad types of presentation. Many of these rashes have a broad differential diagnosis. However, it is important to consider COVID-19, especially in the patient with upper respiratory or systemic symptoms (Table 1) . J o u r n a l P r e -p r o o f There are multiple reports of patients presenting with a maculopapular rash, characterized by erythematous macules covered with small papules, or with large plaques (Figure 1 ). [15, [17] [18] [19] The rash may also be perifollicular and associated with scaling and confluence, which may cause it to be mistaken for pityriasis rosea. [20] This type of rash has been suggested to have a mean duration of approximately 9 days. [20] One study of 88 patients in Italy found that a maculopapular rash was present in 14 patients (16%). [9] There are several descriptions of the rash in the literature. Four case reports comprising 7 patients described this as diffuse. [14, 18, 21, 22] Some have identified this most commonly on the limbs and trunk. [23] [24] [25] [26] Others have described this on the face [12] or bilateral heels. [27] Two studies have described this as centrifugal in nature, initially starting in the periumbilical or trunk region before spreading distally. [15, 25] J o u r n a l P r e -p r o o f COVID-19. One study by Recalcati found urticaria in 3 of 88 COVID-19 patients. [9] There have been other reports of urticaria affecting various regions of the body in patients of all age groups infected with COVID-19. These cases describe involvement of the trunk, extremities, and head, as well as rash migration, with sparing of the palms and soles. [10, 12, 17, 25, 26, [28] [29] [30] [31] One of the largest series of 73 COVID-19 positive patients with urticaria found that the trunk was most commonly involved, and pruritus occurred in 92% of cases. [20] The mean duration of symptoms was 6.8 days. [20] This study also found that urticaria generally occurred concomitantly with other symptoms in the majority of cases and was associated with more severe disease in this study, with a 2% mortality rate in this population. [20] Vesicular Vesicular rashes include small, fluid-filled blisters, often on an erythematous base (Figure 3 ). [17, 32] with one discussing diffuse involvement of the face and limbs in an 8-year-old. [11] A separate case series found that the vesicular rash occurred for a mean duration of 10.4 days, with vesicles appearing mostly on the trunk and extremities. [20] They also noted that the lesions appeared small and monomorphic as opposed to chickenpox and had hemorrhagic content. [20] In most cases, the vesicular rash preceded other symptoms. [20] J o u r n a l P r e -p r o o f describing this in the literature. One case report described a patient with petechiae who was initially misdiagnosed as dengue fever (in an endemic area), but later discovered to have COVID-19. [33] In this case, the patient was also noted to be significantly thrombocytopenic. [33] Another case described a patient with extensive purpura isolated to flexural areas. [34] Thrombocytopenia is not a common complication in COVID-19, so this may reflect a less common complication, or the rash may be due to an alternate etiology such as vasculitis. Chilblains (also known as pernio or perniosis) is an abnormal response to cold, wherein distal arteries and veins constrict, which can lead to pruritic and tender wounds on the extremities ( Figure 5 ). Patients can present with erythematous or violaceous papules and macules, bullae, or digital swelling. [35] This has been increasingly recognized in association with COVID-19. There have been nearly 100 cases of chilblains associated with COVID-19 already described in the literature. [17, 20, 35, 36] Galván Casas et al. described 71 cases which had a mean duration of 12.7 days. [20] The authors noted that it typically presented in the hands or feet and was usually asymmetrical. [20] Thirty-two percent of cases were painful and 30% had associated pruritus. [20] Compared with other rashes, chilblains typically occurred later in the disease course and after other symptoms had presented. [20] The authors also noted that this was more common in younger patients (mean age 32 years) than the other rashes in their study. [20] This was also evidenced by Recalcati who described 14 cases occurring in mostly children and young adults. Clinical Characteristics of Coronavirus Disease 2019 in China Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. 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