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.

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.

Erythema multiforme-like lesions in children and COVID-19.

During examination of cases of chilblains in children and adolescents, we identified four patients who also showed skin lesions similar to erythema multiforme (EM). They had no other known triggers for EM. One of them had a positive PCR for SARS-CoV-2, while the other three were negative. Skin biopsies from two patients showed features not typical of EM, such as deep perivascular and perieccrine infiltrate and absence of necrosis of keratinocytes. Immunohistochemistry for SARS-CoV/SARS-CoV-2 spike protein showed granular positivity in endothelial cells and epithelial cells of eccrine glands in both biopsies. All patients had an excellent outcome, and had minimal or no systemic symptoms. The coincidence of EM, a condition commonly related to viruses, and chilblains in the setting of COVID-19, and the positivity for SARS-CoV/SARS-CoV-2 spike protein by immunohistochemistry strongly suggest a link between EM-like lesions and SARS-CoV-2.

HSV-associated erythema multiforme in a patient after hematopoietic stem cell transplantation.

Herpes simplex virus (HSV)-associated erythema multiforme (HAEM) is an acute and self-limiting mucocutaneous hypersensitivity reaction triggered by herpes virus infections. We reported a patient with HAEM after hematopoietic stem cell transplantation (HSCT). A 55-year-old man received HSCT 7 months ago. He suffered from chronic graft versus host disease 4 months after HSCT and was treated with prednisone and tacrolimus. One week ago, he developed generalized macules with leukopenia. Dermatological examination revealed multiple iris-like erythemas on his trunk and extremities. The skin lesions and leukopenia resolved upon anti-HSV treatment.

Erythema multiforme: Differences between HSV-1 and HSV-2 and management of the disease-A case report and mini review.

Erythema multiforme (EM) is an immune-mediated reaction characterized by target lesions and with possible mucosal involvement. Its most frequent cause is HSV, with HSV-1 more common than -2. It is usually self-limited but it can show recurrences. We report a peculiar case of recurrent herpes-associated erythema multiforme (HAEM) in a 35-year-old man. The patient was affected by both herpes labialis and genitalis, but the typical target lesions were only associated with recurrent herpes labialis. Here, we hypothesize about the pathogenic differences between HSV-1 and HSV-2, and discuss the therapeutic management of HAEM.

Efficacy of interferon in recurrent valaciclovir-refractory erythema multiforme in a patient not infected with hepatitis C virus.

Recurrent erythema multiforme (EM) is rare and is most typically related to infections with herpes simplex virus. Prophylactic administration of valaciclovir is the first-line treatment, but there is no agreement about second-line treatment in cases of ineffectiveness. We present a 31-year-old man who was not infected with hepatitis C virus (HCV), and had a history of severe and recurrent EM, unresponsive to valaciclovir, colchicine and hydroxychloroquine. The patient noticed that an intermittent flu-like illness seemed to have abrogated an EM flare. Because of this observation, the next EM flares were treated with short courses of interferon, which gave rapid and complete efficacy. Efficacy of interferon in EM has only been reported in two previous patients, in whom the drug was administered to treat HCV infection. Efficiency was attributed to treatment of the underlying HCV infection, which was thought to be the origin of EM in both cases. This is the first case, to our knowledge, reporting a dramatic response to interferon-alfa in a patient who was not infected with HCV.

Postherpetic Nevocentric Erythema Multiforme.

A previously healthy 35-year-old Caucasian woman presented with abrupt onset of erythematous, mildly pruritic plaques surrounding the majority of the nevi present on her neck, chest, back, and upper and lower extremities. She denied history of any recent systemic illnesses and was not taking any medications. On further questioning, the patient reported a recent episode of recurrent herpes labialis 2 weeks prior. The patient has a Fitzpatrick type I skin type with more than 100 brown and reddish brown pigmented macules and papules over her entire body. Plaques ranged in size from 0.4 cm to 1.5 cm depending on the size of the corresponding nevus. The patient's skin was examined in its entirety, and there were no lesions suspicious for melanoma. Two biopsies were performed from the patient's back: one from the nevus itself and another from the surrounding erythematous plaque. The nevocentric erythematous plaques were visible for approximately 1 week at which time they gradually disappeared without treatment. As these areas improved, the patient noticed targetoid lesions on the dorsal hands without associated nevi. Two weeks later, the targetoid lesions had spontaneously resolved.

The use of corticosteroids in management of Herpes associated Erythema Multiforme.

Erythema multiforme (EM) is an acute self-limiting condition considered to be hypersensitivity reaction associated commonly with infections or medications. It is characterized by skin lesions, with oral or other mucous membrane involvement. Occasionally EM may involve the mouth alone. We report a ten year-old healthy male child who developed skin lesions of both palms and soles associated with oral ulcerative lesions. The patient first noticed the lesions on the palms and soles followed by involvement of the oral cavity in form of multiple haemorrhagic crusting ulcerations involving lips and buccal mucosa. The diagnosis was established clinically based on the signs and symptoms as erythema multiforme minor associated with herpes simplex infection. Systemic corticosteroids as a treatment modality should always be considered for the treatment of erythema multiforme minor.

Risk factors and mortality among patients with severe muco-cutaneous drug reactions.

INTRODUCTION: The aim of this study was to examine risk factors and mortality among patients with erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). METHODS: This was a retrospective evaluation of the med-ical records of 250 patients from two Danish tertiary dermatological departments during a ten-year period. RESULTS: In a total of 192 cases (77.4%), the primary diagnosis of EM (66.5%), SJS (62.2%) and TEN (100%) was confirmed, whereas the remaining cases (22.6%) were diagnosed differently. Antibiotics and allopurinol were predominantly associated with TEN, whereas SJS was associated with a broad spectrum of drugs. EM was related mainly to viral infections, predominantly herpes (30.6%); 38.2% of the causes of EM remained unknown. Patients with TEN had the highest mortality; i.e. 60% in the course of the ten-year study period: adjusted hazard ratio (HR) = 11.2 (95% confidence interval (CI): 3.65-34.35); p < 0.001 compared with EM patients. The risk of death was also increased among patients with SJS relative to patients with EM: HR = 2.60 (95% CI: 1.10-6.16); p = 0.030; however, this did not remain statistically significant after adjustment for age, co-morbidity, infection, cancer and polypharmacy, HR = 0.99 (95% CI: 0.38-2.57); p = 0.976. CONCLUSION: We validated diagnoses in 250 patients with EM, SJS and TEN diagnosed during a ten-year period. The survival of patients with TEN was expectedly low compared with patients with EM. We extend previous findings by showing that after adjustment for confounders, the survival rates of SJS and EM are comparable. FUNDING: none. TRIAL REGISTRATION: not relevant.