Dermatopathology of COVID-19 infection and vaccination.

BACKGROUND: Many peculiar skin changes have been described in relation to both coronavirus disease 2019 (COVID-19) infection and vaccination. OBJECTIVE: This paper provides an overview of these dermatologic manifestations, focusing on their dermatopathological appearances. RESULTS: Most COVID-19 patients develop variegated maculopapular eruptions with a combination of histological patterns commonly including keratinocyte apoptosis and eosinophilia. Urticaria-like lesions often show a combination of spongiotic and lichenoid patterns and are more frequent in individuals with severe disease. Vesicular lesions can be disseminated; in some cases, they become pustular and in others show dyskeratosis and a peculiar form of ballooning. Some patients develop vesicular Grover disease on the trunk. Young patients with a strong immunological response can eliminate the virus easily but may develop chilblains as a consequence of the high interferon response. Conversely, older individuals with immunosenescence and a tendency toward hypercoagulability can present livedoid and ischemic areas. Regarding COVID-19 vaccination, hypersensitivity reactions are most frequent, including "COVID-arm." Nonetheless, a combination of local and systemic cutaneous manifestations (reactogenicity) is commonly seen. Histopathologically, lichenoid and spongiotic changes and a variable number of eosinophils are typical of rashes characterized by papules and plaques. Other dermatological side effects of COVID-19 vaccination include lesions mimicking well-defined dermatoses such as lichen planus or bullous pemphigoid and triggering of collagenous diseases. CONCLUSION: Well-characterized skin manifestations of coronavirus disease 2019 (COVID-19) include chilblains, livedo necrotic lesions, vesicular eruptions, urticarial lesions, and maculopapular eruptions. Hypersensitivity reactions are common after SARS-CoV­2 mRNA vaccination. Vaccine reactions may also mimic other dermatosis such as bullous pemphigoid or lichen planus, stimulate herpes reactivation, or trigger the development of autoimmune diseases.

Urticarial vasculitis: A potential signpost for multisystem inflammatory syndrome in children.

Multisystem inflammatory syndrome in children (MIS-C) is a rare and serious complication of Sars-Cov-2 infection. Dermatologic manifestations are present in the majority of patients. Skin lesions found in children with MIS-C are classified into four categories: morbilliform, reticulated, scarlatiniform, and urticarial lesions. Clinicopathologic characterization within these categories is limited. Thus, we present a clear example of an urticarial lesion in the context of MIS-C with well-documented clinicopathologic phenomena. A previously healthy 16-year-old female presented with 3 weeks of an itchy, burning rash initially presenting on her right forearm (and lasting greater than 24 hours without migration) before spreading diffusely. She also reported fever, cough, myalgias, nausea, and vomiting of 4 weeks' duration. Physical examination revealed an edematous, maculopapular, nonblanching, erythematous rash covering the patient's upper extremities, abdomen, back, anterior thighs, and face. The patient tested positive for COVID-19. A low-grade leukocytoclastic vasculitis was noted along with intraluminal fibrin and rare microthrombi in vessels of the mid to deep dermis. The patient was diagnosed with MIS-C and urticarial vasculitis. She was treated with steroids and naproxen for subsequent MIS-C flares. Dapsone treatment was started for the urticarial vasculitis.

Identification, Mechanism, and Treatment of Skin Lesions in COVID-19: A Review.

Coronavirus disease 2019 (COVID-19) is a multisystem disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), that primarily causes respiratory symptoms. However, an increasing number of cutaneous manifestations associated with this disease have been reported. The aim of this study is to analyze the scientific literature on cutaneous manifestations associated with SARS-CoV-2 by means of a narrative literature review until June 2021. The search was conducted in the following electronic databases: Medline (PubMed), SciELO, and Cochrane Library Plus. The most common cutaneous manifestations in patients with COVID-19 are vesicular eruptions, petechial/purpuric rashes, acral lesions, liveoid lesions, urticarial rash, and maculopapular-erythematous rash. These manifestations may be the first presenting symptoms of SARS-CoV-2 infection, as is the case with acral lesions, vesicular eruptions, and urticaria. In relation to severity, the presence of liveoid lesions may be associated with a more severe course of the disease. Treatment used for dermatological lesions includes therapy with anticoagulants, corticosteroids, and antihistamines. Knowledge of the dermatologic manifestations associated with SARS-CoV-2 contributes to the diagnosis of COVID-19 in patients with skin lesions associated with respiratory symptoms or in asymptomatic patients. In addition, understanding the dermatologic lesions associated with COVID-19 could be useful to establish a personalized care plan.

Cutaneous manifestations associated with SARS-CoV-2: an emerging topic in a pandemic era.

A 70-year-old man was admitted to our COVID-19 ward with thoracalgia, productive mucus cough, fatigue and erythematous-violaceous macules on the inner side of feet and interdigital regions. The patient was started on oxygen and dexamethasone. On the day of discharge, he maintained the skin changes despite the resolution of COVID-19 symptoms. A 57-year-old woman initially presented with diffuse urticarial rash on the cervical and chest region. Oral cetirizine was started, and pruritus improved. Thirty days after the discharge, the patient maintained the rash, but without pruritus. A 49-year-old man was admitted with thoracalgia, shortness of breath, dry cough and urticarial rash on the cervical and chest region. The patient was treated with cetirizine. The pruritus improved, and 5 days after discharge, the urticarial areas completely disappeared.

COVID-19: The experience from Italy.

A wide range of cutaneous signs are attributed to COVID-19 infection. This retrospective study assesses the presence and impact of dermatologic manifestations related to the spread of COVID-19 in Lombardy, the geographic district with the first outbreak in Italy. A cohort of 345 patients with laboratory confirmed COVID-19 was collected from February 1, 2020 to May 31, 2020. Cutaneous signs and dermatologic diagnoses were recorded on admission, and during the course of the disease. Of the 345 patients included in the study, 52 (15%) had new-onset dermatologic conditions related to COVID-19. We observed seven major cutaneous clinical patterns, merged under 3 main groups: Exanthems, vascular lesions, and other cutaneous manifestations. Each subset was detailed with prevalence, age, duration, prognosis, and histology. Cutaneous findings can lead to suspect COVID-19 infection and identify potentially contagious cases with indolent course.

Clinicopathologic correlations of COVID-19-related cutaneous manifestations with special emphasis on histopathologic patterns.

Skin is one of target organs affected by the novel coronavirus SARS-CoV-2, and in response to the current COVID-19 pandemic, a fast body of literature has emerged on related cutaneous manifestations. Current perspective is that the skin is not only a bystander of the general cytokines storm with thrombophilic multiorgan injury, but it is directly affected by the epithelial tropism of the virus, as confirmed by the detection of SARS-CoV-2 in endothelial cells and epithelial cells of epidermis and eccrine glands. In contrast with the abundance of epidemiologic and clinical reports, histopathologic characterization of skin manifestations is limited. Without an adequate clinicopathologic correlation, nosology of clinically similar conditions is confusing, and effective association with COVID-19 remains presumptive. Several patients with different types of skin lesions, including the most specific acral chilblains-like lesions, showed negative results at SARS-CoV-2 nasopharyngeal and serologic sampling. The aim of this review is to provide an overview of what has currently been reported worldwide, with a particular emphasis on microscopic patterns of the skin manifestations in patients exposed to or affected by COVID-19. Substantial breakthroughs may occur in the near future from more skin biopsies, improvement of immunohistochemistry studies, RNA detection of SARS-CoV-2 strain by real-time polymerase chain reaction-based assay, and electron microscopic studies.

COVID-19: The experience from Beijing, China.

The epidemiology of coronavirus disease 2019 (COVID-19) in Beijing, China, is summarized. This presentation highlights its main clinical manifestations, including the skin findings in Beijing and sums up the cutaneous damage to the medical staff in their epidemic preventative work. Although there had been few COVID-19 patients who reported skin lesions in Beijing and even in China, dermatologists still needed to pay attention to self-protection in their daily work. Skin damage caused by protective equipment is very common in the majority of the medical staff in Beijing.

Severe urticarial rash as the initial symptom of COVID-19 infection.

A 54-year-old woman presented with pruritic rash and hives of 3 days' duration followed by shortness of breath for 1 day. SARS-CoV-2 PCR test for COVID-19 was positive. Cutaneous manifestations of COVID-19 include acral lesions, urticarial rash, erythematous maculopapular rash, vascular rashes and vesicular rash. The cutaneous manifestations are mostly described as self-limiting. Urticarial rashes are not reported as the initial presentation symptom of COVID-19 infection but mostly noted to occur at the same time or after the onset of non-cutaneous symptoms. Management of cutaneous manifestations of COVID-19 affecting quality of life has not been well studied. Antihistamine therapy is the primary recommended therapy. Role of antiviral therapy for severe cases of rash needs to be further assessed.

Severe Acute Thromboinflammation: Case Report of Individualized Homeopathic Treatment.

Thromboinflammation is a still not well-understood phenomenon, which has recently come to the foreground as a function of its relevance in the pathophysiology of coronavirus disease 2019 (COVID-19). The patient described in the present case report exhibited acute fever, giant urticaria, elevated acute phase reactants, and very high d-dimer levels, thus characterizing thromboinflammation. She was diagnosed as a COVID-19 suspect case, which was not confirmed; urticarial vasculitis was ruled out. Homeopathic treatment was started with the earliest clinical manifestations, resulting in rapid and drastic reduction of inflammation and hypercoagulability within the first 12 hours, and full recovery on 10-day follow-up assessment. This case demonstrates the effectiveness of homeopathy in a severe acute disorder, and points to the need to include laboratory testing in homeopathic clinical assessment to achieve an accurate picture of disease, and to avoid the risk of passing over life-threatening disorders.

Acute urticaria preceding other COVID-19-associated manifestations-A case report.

The novel coronavirus SARS-CoV-2 has been associated with a variety of dermatologic manifestations, often the predominant finding in otherwise asymptomatic or oligosymptomatic patients. Urticarial eruption is one example, but few cases have been reported among pediatric patients. We present a case of acute urticaria in a 6-month-old boy preceding other COVID-19 symptoms. The suspicion of a possible COVID-19-associated cutaneous manifestation prompted timely testing and diagnosis of SARS-CoV-2 infection.

Skin Manifestations Associated with COVID-19: Current Knowledge and Future Perspectives.

BACKGROUND: Coronavirus disease-19 (COVID-19) is an ongoing global pandemic caused by the "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2), which was isolated for the first time in Wuhan (China) in December 2019. Common symptoms include fever, cough, fatigue, dyspnea and hypogeusia/hyposmia. Among extrapulmonary signs associated with COVID-19, dermatological manifestations have been increasingly reported in the last few months. SUMMARY: The polymorphic nature of COVID-19-associated cutaneous manifestations led our group to propose a classification, which distinguishes the following six main clinical patterns: (i) urticarial rash, (ii) confluent erythematous/maculopapular/morbilliform rash, (iii) papulovesicular exanthem, (iv) chilblain-like acral pattern, (v) livedo reticularis/racemosa-like pattern, (vi) purpuric "vasculitic" pattern. This review summarizes the current knowledge on COVID-19-associated cutaneous manifestations, focusing on clinical features and therapeutic management of each category and attempting to give an overview of the hypothesized pathophysiological mechanisms of these conditions.

Skin manifestations of COVID-19 in children: Part 2.

The current COVID-19 pandemic is caused by the SARS-CoV-2 coronavirus. The initial recognized symptoms were respiratory, sometimes culminating in severe respiratory distress requiring ventilation, and causing death in a percentage of those infected. As time has passed, other symptoms have been recognized. The initial reports of cutaneous manifestations were from Italian dermatologists, probably because Italy was the first European country to be heavily affected by the pandemic. The overall clinical presentation, course and outcome of SARS-CoV-2 infection in children differ from those in adults, as do the cutaneous manifestations of childhood. In this review, we summarize the current knowledge on the cutaneous manifestations of COVID-19 in children after thorough and critical review of articles published in the literature and from the personal experience of a large panel of paediatric dermatologists in Europe. In Part 1, we discussed one of the first and most widespread cutaneous manifestations of COVID-19, chilblain-like lesions. In this part of the review, we describe other manifestations, including erythema multiforme, urticaria and Kawasaki disease-like inflammatory multisystemic syndrome. In Part 3, we discuss the histological findings of COVID-19 manifestations, and the testing and management of infected children for both COVID-19 and any other pre-existing conditions.

Skin manifestations of COVID-19 in children: Part 3.

The current COVID-19 pandemic is caused by the SARS-CoV-2 coronavirus. The initial recognized symptoms were respiratory, sometimes culminating in severe respiratory distress requiring ventilation, and causing death in a percentage of those infected. As time has passed, other symptoms have been recognized. The initial reports of cutaneous manifestations were from Italian dermatologists, probably because Italy was the first European country to be heavily affected by the pandemic. The overall clinical presentation, course and outcome of SARS-CoV-2 infection in children differ from those in adults as do the cutaneous manifestations of childhood. In this review, we summarize the current knowledge on the cutaneous manifestations of COVID-19 in children after thorough and critical review of articles published in the literature and from the personal experience of a large panel of paediatric dermatologists in Europe. In Part 1, we discuss one of the first and most widespread cutaneous manifestations of COVID-19, chilblain-like lesions, and in Part 2 we expanded to other manifestations, including erythema multiforme, urticaria and Kawasaki disease-like inflammatory multisystemic syndrome. In this part of the review, we discuss the histological findings of COVID-19 manifestations, and the testing and management of infected children for both COVID-19 and any other pre-existing conditions.

A case for palliative dermatology: COVID-19-related dermatoses.

The unprecedented coronavirus disease 2019 (COVID-19) pandemic has challenged health care systems in different ways. In the United Kingdom, various subspecialties are deployed to the wards to help medical workforce in the frontlines, with dermatologists helping with general medical wards and on-calls. We present a case of COVID-19-related urticaria manifesting in a palliative setting and responding well to systemic antihistamine. This pandemic has highlighted a new subspecialty that should be explored and researched-palliative dermatology-bridging elements of dermatology with the concepts of palliative medicine. As dermatologists, we should be in the position to help with the last stages of a patient's journey.

Urticaria and COVID-19: A review.

The first cases of the coronavirus disease (COVID-19) appeared in Wuhan, China, in December 2019. COVID-19 was declared a pandemic in March 2020. Cutaneous manifestations are among the heterogenous clinical features of the disease, and urticaria is one of the most common skin manifestations reported in COVID-19. We reviewed the literature available regarding COVID-19-associated urticaria. A literature search in the PubMed and Scopus databases was conducted, till the cut-off date of 24th July 2020, using the following terms: "skin" or "cutaneous" or "urticaria" or "urticarial," and "COVID-19" or coronavirus disease. The search resulted in 502 publications. In this review, 30 articles with a total of 202 patients with COVID-19-associated urticaria were included. Patient age ranged from 2 months to 84 years. Gender was reported in 149 patients; of these 96 (64%) were females, and 53 (36%) were males. Of the 105 patients with a determined onset of the disease, 58 (55%) presented with rash preceding or concurrently with the classic COVID-19 symptoms. Urticarial rash was mainly either generalized or distributed on the trunk. Associated respiratory symptoms, level of care, medications used, comorbidities, and duration, and distribution and timeline of urticarial rash were summarized. In this article, we present a review of literature on COVID-19-associated urticaria, which would enable dermatologists and other clinicians to diagnose COVID-19 early in the onset of disease, and prevent viral spread. Additionally, this may also pave the way for further studies on this topic.

Skin manifestations in patients hospitalized with confirmed COVID-19 disease: a cross-sectional study in a tertiary hospital.

BACKGROUND: COVID-19 cutaneous manifestations have been recently described and classified in five different clinical patterns, including acral erythema-edema (pseudo-chilblain), maculopapular exanthemas, vesicular eruptions, urticarial lesions, and livedo or necrosis. OBJECTIVES: The objective of this study was to examine the skin of hospitalized patients with a confirmed diagnosis of COVID-19 disease and describe the real prevalence of skin manifestations. METHODS: A cross-sectional study, which included hospitalized patients in Cruces University Hospital from April 14-30, 2020, with a laboratory-confirmed diagnosis of COVID-19 (with polymerase chain reaction and/or serology tests), was conducted. Entire body surface examination was performed by experienced dermatologists to search for cutaneous manifestations related to COVID-19 disease. RESULTS: From a sample of 75 patients, 14 (18.7%) developed cutaneous manifestations possibly related to COVID-19. We found six patients with acral erythema-edema (pseudo-chilblain) (42.8%), four patients with maculopapular exanthemas (28.6%), two patients with urticarial lesions (14.3%), one patient with livedo reticularis-like lesions (7.15%), and one patient with vesicular eruption (7.15%). CONCLUSIONS: Our study provides a more plausible relationship between the main cutaneous patterns and COVID-19 in hospitalized patients as all of them had a confirmatory laboratory test. Skin manifestations are frequent but mild with spontaneous resolution. These findings are nonspecific and can be similar to other viral infections and adverse drug reactions in hospitalized patients.

Covid-19 pandemic and the skin.

In the beginning of the COVID-19 outbreak, skin manifestations, if present, were not paid enough attention. Then, the focus moved toward the impact of the prolonged use of personal protective measures in both healthcare workers and patients. In the meantime, attention is increasingly paid to dermatology as a result of the concern for certain groups of dermatologic patients, including those whose condition may worsen by the thorough disinfection measures and those treated with immunosuppressants or immunomodulators. Following patients with psoriasis on biological therapy, as well as other inflammatory and autoimmune cutaneous disorders such as atopic dermatitis, pemphigus, pemphigoid diseases, and skin cancer provoked the interest of dermatologists. Finally, an intriguing question to the dermatologic society was whether skin changes during COVID-19 infection exist and what could be their diagnostic or prognostic value. Here, we summarize skin conditions during the COVID-19 pandemic, patient information, and expert recommendations and give an overview about the registries launched to document skin changes during COVID-19, as well as details about certain patient groups infected with SARS-CoV-2, for example, psoriasis, atopic dermatitis, and autoimmune bullous diseases.

Review of adverse cutaneous reactions of pharmacologic interventions for COVID-19: A guide for the dermatologist.

The new coronavirus, severe acute respiratory syndrome coronavirus 2, is associated with a wide variety of cutaneous manifestations. Although new skin manifestations caused by COVID-19 are continuously being described, other cutaneous entities should also be considered in the differential diagnosis, including adverse cutaneous reactions to drugs used in the treatment of COVID-19 infections. The aim of this review is to provide dermatologists with an overview of the cutaneous adverse effects associated with the most frequently prescribed drugs in patients with COVID-19. The skin reactions of antimalarials (chloroquine and hydroxychloroquine), antivirals (lopinavir/ritonavir, ribavirin with or without interferon, oseltamivir, remdesivir, favipiravir, and darunavir), and treatments for complications (imatinib, tocilizumab, anakinra, immunoglobulins, corticosteroids, colchicine and low molecular weight heparins) are analyzed. Information regarding possible skin reactions, their frequency, management, and key points for differential diagnosis are presented.

Case report: SARS-CoV-2-induced urticaria or just a concomitance?

The association between urticaria and different virus infections has been reported in many studies. Different virus infections have been reported to be comorbidities of spontaneous urticaria. In this paper, we report the case of a male patient with acute urticaria 7 days after he left the hospital where he was treated for coronavirus disease 2019 (COVID-19). This infection may act as a causative or a facilitating factor for the initiation of acute urticaria and additional cofactors such as stress may contribute for the urticaria phenotype to be expressed. Additional facts for severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) virus in future will clarify if urticarial rash is one of the COVID's multiple faces.

What the physicians should know about mast cells, dendritic cells, urticaria, and omalizumab during COVID-19 or asymptomatic infections due to SARS-CoV-2?

Coronavirus disease (COVID-19) pandemic presents several dermatological manifestations described in the present indexed literature, with around 700 cases reported until May 2020, some described as urticaria or urticarial rashes. Urticaria is constituted by evanescent erythematous-edematous lesions (wheals and flare), which does not persist in the same site for more than 24 to 48 hours and appears in other topographic localization, resolving without residual hyper pigmentation. During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, some cytokines are synthesized, including Interferon (IFN) type I, TNF-α, and chemokines which may induce mast cells (MCs) and basophils degranulation by mechanisms similar to the autoinflammatory monogenic or polygenic diseases. In this article, we discuss the spectrum of the urticaria and urticarial-like lesions in the COVID-19's era, besides other aspects related to innate and adaptative immune response to viral infections, interactions between dermal dendritic cells and MCs, and degranulation of MCs by different stimuli. Plasmacytoid dendritic cells share, in allergic patients, expression of the high-affinity IgE receptors on cell membranes and demonstrated a low pattern of type I IFN secretion in viral infections. We discuss the previous descriptions of the effects of omalizumab, a monoclonal antibody directed to IgE and high-affinity IgE receptors, to improve the IFN responses and enhance their antiviral effects.