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.

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.

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.

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.

[Erythema exudativum multiforme--case report]. / Rumien wysiekowy wielopostaciowy--opis przypadku.

Erythema exudativum multiforme (EM) is an acute mucocutaneous disease. Etiology of this disease is not clear. 50% - 60% cases of EM is induced by HSV infection (herpes simplex virus 1, herpes simplex virus 2). EM lesions may appear as red macules, erosions, ulcerations and hemorrhagic crusts. The study describes the case of 22 - year - old male who had characteristic lesions for EM after HSV infection.

Acute skin graft-versus-host disease with molecular features mimicking herpes simplex virus-associated erythema multiforme: report of three cases.

BACKGROUND: Acute skin erythematous lesions that follow allogeneic hematopoietic stem cell transplantation (HSCT) and are histologically diagnosed as graft-versus-host disease (GVHD) are often associated with reactivation of latent herpes simplex virus (HSV). OBJECTIVE: To further examine the relationship between reactivated HSV and GVHD development. METHODS: We present 3 patients with acute skin GVHD after allogeneic HSCT who were studied prospectively for expression of the HSV antigen Pol, which is involved in HSV-associated erythema multiforme. RESULTS: Pol was expressed in the GVHD lesions but not the pre-HSCT normal skin or peripheral blood mononuclear cells. Lesion severity correlated with the Pol levels but not the histopathologically defined GVHD grade. Lesion development was accompanied by increased numbers of Pol+ circulating/skin-infiltrating CD34+ stem cells and CD1a+ and other dermal dendritic cells. CONCLUSIONS: Subclinical HSV infection of circulating CD34+ cells can contribute to some post-HSCT skin lesions histologically diagnosed as GVHD, with potential preventive and therapeutic implications.

Frequent detection of herpes simplex virus antigen in skin and peripheral blood CD34+ mononuclear cells from patients with graft-versus-host disease.

Viruses are implicated in the initiation or flare of graft-versus-host disease (GVHD) by virtue of their ability to activate antigen-presenting dendritic cells (DC). Herpes simplex virus (HSV) infects circulating CD34+ stem cell progenitors, favoring their differentiation into skin homing DC (CD1a+ Langerhans cells) that contribute to the development of an inflammatory skin rash known as HSV-associated erythema multiforme (HAEM). Following on these findings, we conducted a prospective study to examine whether HSV is also associated with GVHD. Skin biopsies and peripheral blood mononuclear cells (PBMC) were collected from 37 consecutive patients on admission before and after allogeneic hematopoietic stem cell transplantation (HSCT) and examined for HSV antigen (Pol) expression and the presence of Pol+CD34+ and Pol+CD1a+ cells. Sixteen patients developed a skin rash that was histopathologically consistent with GVHD (group I), 3 patients had a rash that was not GVHD (group II, EM-like) and 18 patients did not develop any rash after HSCT (group III). Skin biopsies from the group I patients were Pol negative pre-HSCT (baseline) but became Pol+ after the diagnosis of GVHD. The GVHD biopsies also contained Pol+CD34+ and Pol+CD1a+ cells, and these patients had a significant percentage of circulating Pol+CD34+ and Pol+CD1a+ PBMC. By contrast, the group II patients had Pol+ skin cells and Pol+CD34+ circulating PBMC at baseline that decreased post-HSCT. The group III patients had Pol negative skin and very few circulating Pol+CD34+ and Pol+CD1a+ PBMC at baseline that were not significantly changed post-HSCT. The data associate skin GVHD with HSV reactivation during conditioning and its propensity for nonreplicative infection of CD34+ PBMC that induces DC activation. Further studies are needed to better elucidate this association.

Diagnosis of herpes simplex virus-induced erythema multiforme confounded by previous infection with Mycoplasma pneumonia.

Erythema multiforme (EM) is an immune-mediated hypersensitivity reaction often related to viral infection or medications. Infection-induced EM is typically self-limited and commonly caused by herpes simplex virus (HSV) or Mycoplasma pneumoniae (MP); recurrent EM is almost always associated with HSV. We present a concise overview of diagnostic techniques for HSV and MP, as repeatedly elevated MP titers in our case led to a delayed diagnosis of HSV-induced EM.

Erythema multiforme in a newborn associated with acute acquired cytomegalovirus infection.

Erythema multiforme is exceptional in newborns, and none of the few available reports has revealed a clear etiologic agent, not even herpes simplex virus. Immunocompetent patients rarely present with cutaneous cytomegalovirus involvement, and few cases of cytomegalovirus-associated erythema multiforme have been described, none of them in newborns. We report the first case of erythema multiforme in a newborn associated with cytomegalovirus infection.

Multiple finger nodules and an erythematous rash - a case study.

CASE STUDY: A previously well male, 18 years of age, from a rural community, presented with three painful, itchy nodules on the fingers of his left hand, which had been present for 1 week. He had been prescribed amoxicillin clavulanate but presented again when there was no improvement after 4 days of taking antibiotics. Examination revealed three erythematous and umbilicated nodules without any halo, but with a central depression with exudate (Figure 1a). No specific treatment was instituted at this visit. One week later the patient re-presented with new erythematous lesions on the palms and dorsum of his hands. The original three lesions had improved and were drier than previously (Figure 1b, c). The new lesions disappeared after 2 weeks and the original lesions after 4 weeks, without any other treatment.

Transient natural killer deficiency in a boy with herpes simplex virus-associated recurrent erythema multiforme.

Erythema multiforme is characterized by itching macules, papules and bullae, symmetrically distributed on the dorsum of the hands. They can follow the administration of several drugs or infections with various agents, and in particular with herpes simplex virus. The recurrent variant is very rare, especially in the paediatric age group. We describe the case of a male adolescent with recurrent erythema multiforme caused by herpes virus and transient natural killer deficiency.

Erythema multiforme photoinduced by paroxetine and herpes simplex virus.

Erythema multiforme (EM) is a self-limited skin disease, characterized by the abrupt onset of symmetric red papules that may evolve into target lesions often precipitated by an infection. Photosensitive erythema multiforme (PEM) is a rare disorder characterized by the distribution of the lesions on sun-exposed areas. It has been described at the sites of sunburn, following episodes of polymorphic light eruption or herpes labialis and in association with drugs. To our knowledge, PEM photoinduced by selective serotonin reuptake inhibitors has not been reported. We describe a patient who had two consecutive episodes of PEM related to two different triggers: paroxetine and HSV infection. In the first episode, systemic photosensitivity was confirmed with the photobiological study. UVB-MED was decreased when the patient was taking paroxetine and did not change after its substitution for duloxetine. However, it became normal after the withdrawal of both drugs, suggesting a cross-reactivity reaction. The UVB photopatch test with paroxetine was positive. The second episode occurred after a herpes labialis relapse. At that time, UVB-MED was normal.