SARS-CoV-2 detection by digital polymerase chain reaction and immunohistochemistry in skin biopsies from 52 patients with different COVID-19-associated cutaneous phenotypes.

BACKGROUND: COronaVIrus Disease 19 (COVID-19) is associated with a wide spectrum of skin manifestations, but SARS-CoV-2 RNA in lesional skin has been demonstrated only in few cases. OBJECTIVE: To demonstrate SARS-CoV-2 presence in skin samples from patients with different COVID-19-related cutaneous phenotypes. METHODS: Demographic and clinical data from 52 patients with COVID-19-associated cutaneous manifestations were collected. Immunohistochemistry and digital PCR (dPCR) were performed in all skin samples. RNA in situ hybridization (ISH) was used to confirm the presence of SARS-CoV-2 RNA. RESULTS: Twenty out of 52 (38%) patients presented SARS-CoV-2 positivity in the skin. Among these, 10/52 (19%) patients tested positive for spike protein on immunohistochemistry, five of whom had also positive testing on dPCR. Of the latter, one tested positive both for ISH and ACE-2 on immunohistochemistry while another one tested positive for nucleocapsid protein. Twelve patients showed positivity only for nucleocapsid protein on immunohistochemistry. CONCLUSIONS: SARS-CoV-2 was detected only in 38% of patients, without any association with a specific cutaneous phenotype, suggesting that the pathophysiology of cutaneous lesions mostly depends on the activation of the immune system. The combination of spike and nucleocapsid immunohistochemistry has higher diagnostic yield than dPCR. Skin persistence of SARS-CoV-2 may depend on timing of skin lesions, viral load and immune response.

The clinical and pathologic spectrum of mucocutaneous reactions after COVID-19 vaccinations in three tertiary referral centers of northern Italy.

Adverse cutaneous reactions after COVID-19 vaccinations have increased, highlighting not only how SARS-CoV-2 infection but also COVID-19 vaccines may induce adverse cutaneous manifestations. We evaluated the clinical and pathologic spectrum of mucocutaneous reactions after COVID-19 vaccinations, observed consecutively within three large tertiary centers of the Metropolitan City of Milan (Lombardy), comparing our results with the currently available literature. We retrospectively reviewed medical records and skin biopsies of patients diagnosed with mucocutaneous adverse events after COVID-19 vaccinations and followed at three Italian tertiary referral centers in the Metropolitan City of Milan. One hundred twelve patients (77 women and 35 men (112 total); median age, 60 years) have been included in the present study; a cutaneous biopsy was performed in 41 cases (36%). The trunk and arms were the most involved anatomic areas. Autoimmune reactions after COVID-19 vaccinations, urticaria, morbilliform eruptions, and eczematous dermatitis have been the most commonly diagnosed disorders. Compared to the currently available literature, we performed many more histologic examinations, allowing us to make more precise diagnoses. Most of the cutaneous reactions were self-healing and/or responded to topical and systemic steroids and systemic antihistamines, thus not discouraging the general population from carrying out vaccinations, which currently have a good safety profile.

Clinicopathologic features among different viral epidemic outbreaks involving the skin.

The current coronavirus disease 2019 pandemic has exceeded any epidemiologic prevision, but increasing information suggests some analogies with the major viral outbreaks in the last century, and a general warning has been issued on the possibility that coinfections can make the differential diagnosis and treatment difficult, especially in tropical countries. Some reports have noted that the presence of high dengue antibodies can give a false-negative result when testing for severe acute respiratory syndrome coronavirus 2. Mucocutaneous manifestations are very frequent, with an apparent overlap among different pathogens. However, strong clinicopathologic correlation might provide some clues to address differentials. Waiting for laboratory and instrumental results, the timing and distribution of skin lesions is often pathognomonic. Histopathologic findings characterize certain reaction patterns and provide insights on pathogenetic mechanisms. Unfortunately, skin assessment, especially invasive examinations such as biopsy, takes a back seat in severely ill patients. A literature retrieval was performed to collect information from other epidemics to counteract what has become the most frightening disease of our time.

A definite case of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) induced by administration of the Pfizer/BioNTech BNT162b2 vaccine for SARS-CoV2.

At the end of December 2020, the anti-SARS-CoV2 vaccination campaign began in Italy. As the number of vaccinated subjects in the general population has increased, several adverse reactions have been observed and reported. Severe cutaneous adverse reactions (SCARs) induced by drugs or vaccines are rare but distinguished by high mortality and include DRESS syndrome or drug induced hypersensitivity syndrome (DiHS), a condition characterized by skin rash, eosinophilia, fever, lymphadenopathy, and involvement of one or more internal organs. Here we present a definite case of DRESS that occured following the administration of Pfizer/BioNTech COVID 19 vaccine. He required hospitalization and was managed with supportive care, antihistamines, and intravenous steroid.

Italian adaptation of EuroGuiDerm guideline on the systemic treatment of chronic plaque psoriasis.

SIDeMaST (Società Italiana di Dermatologia Medica, Chirurgica, Estetica e delle Malattie Sessualmente Trasmesse) contributed to the development of the present guideline on the systemic treatment of chronic plaque psoriasis. With the permission of EuroGuiDerm, SIDeMaST adapted the guideline to the Italian healthcare context to supply a reliable and affordable tool to Italian physicians who take care of patients affected by moderate to severe plaque psoriasis. The content of the guideline includes general information on the scope and purpose, health questions covered, target users and strength/limitations of the guideline, suggestions for disease severity grading and treatment goals. It presents the general treatment recommendations as well as detailed management and monitoring recommendations for the individual drugs including acitretin, cyclosporine, fumarates, methotrexate, adalimumab, apremilast, brodalumab, certolizumab pegol, etanercept, guselkumab, infliximab, ixekizumab, risankizumab, secukinumab, tildrakizumab and ustekinumab. Moreover, the guideline provides guidance for specific clinical situations such as patient with concomitant psoriatic arthritis, inflammatory bowel disease, a history of malignancies, a history of depression, diabetes, viral hepatitis, disease affecting the heart or the kidneys as well as concomitant neurological disease. Advice on how to screen for tuberculosis and recommendations on how to manage patients with a positive tuberculosis test result are given. It further covers treatment for pregnant women or those with childbearing potential. Information on vaccination, immunogenicity and systemic treatment during the COVID-19 pandemic is also provided.

Clinicopathologic features between different viral epidemic outbreaks involving the skin.

The current coronavirus disease 2019 pandemic has exceeded any epidemiologic prevision, but increasing information suggests some analogies with the major viral outbreaks of the last century. A general warning has been issued on the possibility that coinfections can make differential diagnosis and treatment difficult, especially in tropical countries. Some reports have pointed out that the presence of high Dengue antibodies can give a false-negative result for severe acute respiratory syndrome coronavirus 2. Mucocutaneous manifestations are very frequent, with an apparent overlap among different pathogens. A strong clinicopathologic correlation, however, may provide some clues to address the differential. Waiting for laboratory and instrumental results, the timing and distribution of skin lesions is often pathognomonic. Histopathologic findings characterize certain reaction patterns and provide insights on pathogenetic mechanisms. Unfortunately, skin assessments, especially invasive exams such as biopsy, are less important in severely ill patients. A literature review was performed to collect information from other epidemics to counteract what has become the most frightening disease of our time.

Risk of infections in psoriasis: assessment and challenges in daily management.

INTRODUCTION: In daily practice management of psoriasis, evaluation of risk factors for infections is having a growing influence. Indeed, in psoriatic patients, risk of infections may be due to psoriasis itself, immunomodulatory therapy, and comorbidities that may increase this risk and patient hospitalization. AREAS COVERED: Given the greater understanding of psoriasis pathogenesis and the increasing number of treatment options, it is particularly important to customize therapy according to each, single patient; psoriasis features and comorbidities are also essential to tailor treatment goals. EXPERT OPINION: In this perspective, the current knowledge on the infectious risk in psoriatic patient, related to comorbidities, such as diabetes mellitus, cardiovascular disease, and chronic obstructive pulmonary, to 'special populations,' to chronic infections, such as latent tuberculosis, chronic hepatitis B and C, and HIV, and to the most recent Covid-19 pandemic scenario, is reviewed and discussed in order to suggest the most appropriate approach and achieve the best available therapeutic option.

Peculiar Histopathologic Feature of an Erythematous/Morbilliform Eruption in a COVID-19-Positive Patient.

ABSTRACT: One of the most common patterns of presentations that have been described in COVID-19 patients includes the erythematous/papular/morbilliform eruptions. However, actually, the diffuse exanthems containing macules and papules were not specific to COVID-19, and even histopathology does not show any specific signs that could help to differentiate COVID-19 skin lesions from non-COVID-19 causes such as drugs or other viral infections. We present the case of a COVID-19-positive woman with a morbilliform rash, whose skin biopsy showed the presence of some peculiar cytopathic epidermal changes that could represent a possible distinctive histopathological feature related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection The presence of viral particles in the keratinocytes with additional positivity of endothelial cells and eccrine glands by immunohistochemistry using an anti-SARS-CoV-2 Spike S1 antibodies supports a causal relation of the lesions with SARS-CoV-2 infection.

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.

The Effect of the COVID-19 Lockdown on Melanoma Diagnosis in Italy.

The coronavirus disease 2019 (COVID-19) pandemic has led to lockdowns for much of the world. In Italy, all health procedures not directly related to COVID-19 were reduced or suspended, thus limiting patient access to hospitals. Any delay in cancer treatment presents the additional risk of tumors progressing from being curable to incurable. Specifically, melanoma survival rate strictly depends on tumor thickness, which, in turn, is a function of time. To estimate the impact on melanoma progression caused by the reduction in dermatologic services during the COVID-19 lockdown, a retrospective observational cohort study was conducted. This study was designed to compare the clinical and histologic characteristics of the primary melanomas removed in the first 2 months after the end of the lockdown (May-July 2020) in 12 Italian centers characterized by different COVID-19 case frequencies. The control group was represented by the melanomas removed during the same period in the previous 3 years. Overall, 1,124 melanomas were considered: 237 as part of the study group and 887 from the control group (average, 295), with a 20% reduction. Breslow thickness, as well as high-risk histotypes and melanomas with vertical growth, increased for all melanomas. Ulcerated and high mitotic index melanomas increased, particularly in northern Italy. In Italy, the lockdown led to a significant worsening of melanoma severity, causing a staging jump, with a consequent worsening of outcomes.

Management of patients with atopic dermatitis undergoing systemic therapy during COVID-19 pandemic in Italy: Data from the DA-COVID-19 registry.

BACKGROUND: Few and small studies have described the management of immunomodulant/immunosuppressive therapies or phototherapy in atopic dermatitis (AD) patients during coronavirus disease 2019 (COVID-19) pandemic. METHODS: A national registry, named DA-COVID-19 and involving 35 Italian dermatology units, was established in order to evaluate the impact of COVID-19 pandemic on the management of adult AD patients treated with systemic immunomodulant/immunosuppressive medications or phototherapy. Demographic and clinical data were obtained at different timepoints by teledermatology during COVID-19 pandemic, when regular visits were not allowed due to sanitary restrictions. Disease severity was assessed by both physician- and patient-reported assessment scores evaluating itch intensity, sleep disturbances, and AD severity. RESULTS: A total of 1831 patients were included, with 1580/1831 (86.3%) continuing therapy during pandemic. Most patients were treated with dupilumab (86.1%, 1576/1831) that was interrupted in only 9.9% (156/1576) of cases, while systemic immunosuppressive compounds were more frequently withdrawn. Treatment interruption was due to decision of the patient, general practitioner, or dermatologist in 39.9% (114/286), 5.6% (16/286), and 30.1% (86/286) of cases, respectively. Fear of increased susceptibility to SARS-CoV-2 infection (24.8%, 71/286) was one of the main causes of interruption. Sixteen patients (0.9%) resulted positive to SARS-CoV-2 infection; 3 of them (0.2%) were hospitalized but no cases of COVID-related death occurred. CONCLUSIONS: Most AD patients continued systemic treatments during COVID pandemic and lockdown period, without high impact on disease control, particularly dupilumab-treated patients.

Syphilis and the COVID-19 pandemic: Did the lockdown stop risky sexual behavior?

Restrictive measures to contain the coronavirus disease 2019 (COVID-19) pandemic might produce different effects on other infective diseases, especially those affecting the most intimate sphere of sexuality. The epidemiology of syphilis could reflect the consequences of whether people are avoiding or not risky behaviors. To understand the course of syphilis during the COVID-19 outbreak, we performed a retrospective observational study of all new diagnoses observed at the STDs Service of the Dermatology Clinic at Cagliari, part of the Italian sentinel surveillance system. All incident cases diagnosed during the first 6 months of each year, from 2016 to 2020, thus including the recent lockdown period, were retrieved from the database. Of the 87 cases studied, 18 occurred during the first 6 months of 2020, almost all patients (88%) presenting with early phases of the disease and reporting unprotected sexual intercourses in spite of community containment and social distancing. Comparison with the previous 4 years found no significant statistical differences that hospital access and management limitations had not impaired the management of patients with syphilis. We alert the medical community of the possible increase of sexually transmitted diseases, as society returns to normal.

Don't forget about syphilis: sexually transmitted diseases during COVID-19 pandemic.

A great heterogeneity of skin manifestations has been increasingly associated with SARS-CoV2 infection, and especially exanthematous eruptions are considered among early presenting signs in symptomatic patients. In this report, a 58-year-old patient presented with fever, generalized rash and systemic symptoms as urgent consultation to the Dermatology Clinic of Cagliari amidst the Italian outbreak in late March 2020. After a negative nasopharyngeal swab for SARS-CoV-2, secondary syphilis was confirmed by serological tests and skin biopsy, underlining that, even during a global pandemic, other common and important diseases should not be overlooked. The case also suggests thought on the ineffectiveness of distancing and social containment measures when dealing with sexually transmitted diseases.

COVID-19-related skin manifestations: Update on therapy.

An increasing body of evidence has been produced in a very limited period to improve the understanding of skin involvement in the current coronavirus 2019 disease pandemic, and how this novel disease affects the management of dermatologic patients. A little explored area is represented by the therapeutic approach adopted for the different skin manifestations associated with the infection. An overview of the current scenario is provided, through review of the English-language literature published until October 30, 2020, and comparison with the personal experience of the authors. As dermatologists, our primary aim is to support patients with the highest standard of care and relieve suffering, even with lesions not life-threatening. With asymptomatic COVID-19 patients, patient discomfort related to skin lesions should not be undervalued and intervention to accelerate healing should be provided. Consensus protocols are warranted to assess the best skin-targeted treatments in COVID-19 patients.

Characteristic of chronic plaque psoriasis patients treated with biologics in Italy during the COVID-19 Pandemic: Risk analysis from the PSO-BIO-COVID observational study.

Background: The susceptibility of patients with chronic plaque psoriasis and the risks or benefits related to the use of biological therapies for COVID-19 are unknown. Few data about prevalence, clinical course and outcomes of COVID-19 among psoriatic patients were reported. The aims of this study were 1) to assess the prevalence and severity of COVID-19 in psoriatic patients treated with biologic agents during the first phase of the emergency (22 February to 22 April 2020) in Italy, and 2) to report the clinical outcomes of patients who have been exposed to individuals with confirmed SARS-CoV-2 infection. Methods: Patients with moderate-to-severe chronic plaque psoriasis, aged ≥18 years and undergoing treatment with biologic agents as of 22 February 2020, were eligible to be included in PSO-BIO-COVID study. Demographic and clinical characteristics of patients using any biologic for psoriasis treatment between 22 February and 22 April 2020 were registered. Results: A total of 12,807 psoriatic patients were included in the PSO-BIO-COVID study. In this cohort 26 patients (0.2%) had a swab confirmation of SARS-CoV-2 infection. Eleven patients required hospitalization and two died. Conclusion: The incidence of COVID-19 observed in our cohort of psoriatic patients (0.2%) is similar to that seen in the general population (0.31%) in Italy. However, the course of the disease was mild in most patients. Biological therapies may likely lessen 'cytokine storm' of COVID-19, which sometimes lead to multiple organ failure, ARDS, and death.