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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-CoV‑2 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., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

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.

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., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: None declared., (Faculty of Homeopathy. This article is published by Thieme.)

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., (© 2020 British Association of Dermatologists.)

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., (© 2020 British Association of Dermatologists.)

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., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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., (© 2020 S. Karger AG, Basel.)

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., Competing Interests: Conflict of interest The authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

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., (© 2020 Wiley Periodicals LLC.)

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., (© 2020 the International Society of Dermatology.)

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., (© 2020 the International Society of Dermatology.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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., (© 2020 Wiley Periodicals LLC.)

Acute infection with viral pathogens in the herpesviridae family can trigger acute urticaria, and reactivation of herpesviridae is associated with cutaneous urticarial-like syndromes such as drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DRESS). Reactivation of latent herpesviridae has not been studied systematically in chronic idiopathic/spontaneous urticaria (CIU). This review proposes that CIU is an inflammatory disorder with autoimmune features (termed 'CVU' for chronic viral urticaria), based on serology consistent with the hypothesis that reactivation of a latent herpesvirus or -viruses may play a role in CIU. Serology obtained from a cohort of omalizumab (Xolair)-dependent patients with severe CIU was consistent with previous HHV-6 infection, persistent viral gene expression and replication. CIU patients also exhibited serological evidence of increased immune response to HHV-4 (Epstein-Barr virus, or EBV) but not all CIU patients were infected with EBV. These observations, combined with case reports of CIU response to anti-viral therapy, suggest that HHV-6, possibly interacting with HHV-4 in cutaneous tissues, is a candidate for further prospective study as a co-factor in CIU., (© 2015 British Society for Immunology.)

Background: Acute and recurrent acute urticaria are often associated with multiple factors including infections and recent data suggest a role for herpesviruses., Objective: To test the null hypothesis, that is, there is no association of herpesvirus infections with urticaria., Methods: Thirty-seven patients between one month and 15 years of age were age matched to 37 controls who were healthy or had mild acute respiratory infections but without urticaria. Patients and controls were followed for 1 to 6 years. Diagnostic studies included DNA detection by real-time PCR for herpes simplex virus (HSV) types 1 and 2, Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human herpesvirus-6 (HHV-6). Tests for other infections included adenovirus, parvovirus B 19, respiratory syncytial virus, influenza A, Group A streptococci, rotavirus, and parasites., Results: Specific infections were diagnosed in 26 of 37 cases and among 9 of 37 control children (P=0.0002). Single or concomitant herpesvirus infections occurred in 24 cases and in 4 controls (65% vs 11 %, p=0.0003). Cases had 10 HHV-6 infections, 8 CMV infections, 5 EBV infections, and 4 HSV-1 infections., Conclusion: Herpesvirus infections are associated with acute or recurrent acute urticaria.

Objective: The main objective of this study was to estimate the prevalence of hepatitis C virus (HCV) infection and to determine the HCV genotypes in urticaria patients of Saudi Arabia., Methods: After thorough clinical examination by a consultant dermatologist, urticaria patients and individual healthy controls were enrolled. Venous blood collected from subjects was analyzed for LFT (aspartate transaminase [AST], alanine transaminase [ALT], albumin, and bilirubin), hepatitis B surface antigen (HBsAg), and HCV antibodies--HCV-RNA-PCR screening and genotyping., Results: Upon enzyme immunoassay (EIA) screening for HCV infection, 5/70 (7.1%) urticaria patients and none among the controls tested positive for the presence of anti-HCV antibodies (p=0.005). Genotyping analysis revealed that HCV belongs to types 3 and 4 with subtypes 3a, 4a, and 4c. No significant variations were seen in the mean serum levels of ALT, AST, albumin, and bilirubin between the patients based on their HCV sero-positivity status., Conclusion: This prospective study indicated that HCV infection plays a significant role in urticaria. However, larger studies in different ethnicities could ascertain the association between different HCV genetic variants and the urticaria.

Many chronic human diseases may have an underlying autoimmune mechanism. In this review, the author presents a case of autoimmune CIU (chronic idiopathic urticaria) in stable remission after therapy with a retroviral integrase inhibitor, raltegravir (Isentress). Previous reports located using the search terms "autoimmunity" and "anti-viral" and related topics in the pubmed data-base are reviewed suggesting that novel anti-viral agents such as retroviral integrase inhibitors, gene silencing therapies and eventually vaccines may provide new options for anti-viral therapy of autoimmune diseases. Cited epidemiologic and experimental evidence suggests that increased replication of epigenomic viral pathogens such as Epstein-Barr Virus (EBV) in chronic human autoimmune diseases such as rheumatoid arthritis (RA), systemic lupus Erythematosus (SLE), and multiple sclerosis (MS) may activate endogenous human retroviruses (HERV) as a pathologic mechanism. Memory B cells are the reservoir of infection of EBV and also express endogenous retroviruses, thus depletion of memory b-lymphocytes by monoclonal antibodies (Rituximab) may have therapeutic anti-viral effects in addition to effects on B-lymphocyte presentation of both EBV and HERV superantigens. Other novel anti-viral therapies of chronic autoimmune diseases, such as retroviral integrase inhibitors, could be effective, although not without risk., (Copyright © 2011 Elsevier B.V. All rights reserved.)

A 34-year-old patient presented with giant, transient urticarial skin lesions and periorbital edema after a 3-month stay in DR Congo. Retrospective analysis of stored samples revealed that these signs were prodromal manifestations of acute hepatitis B infection. The hepatitis B infection was spontaneously cleared; the skin lesion did not recur., (© 2011 International Society of Travel Medicine.)

The role of infectious agents as a cause of chronic idiopathic urticaria (CIU) is uncertain. The objective of this study was to investigate whether genital herpes simplex infection is causally related to CIU. We identified two patients with recurrent genital herpes simplex infections associated with CIU. Episodes of genital herpes were especially associated with acute exacerbation of urticaria. Anti-herpes simplex 2 antibodies and Tzanck smears were done in both patients, along with other relevant investigations for CIU. Acyclovir was added to antihistamine therapy. Both patients were apparently in good health and appeared clinically immunologically stable, though one of them was found to be diabetic. Clinical and laboratory investigations for genital lesions supported a diagnosis of herpes simplex. Anti-herpes simplex 2 antibodies were markedly raised in both patients. The Tzanck smear was positive in one case and negative in the other, despite a definitive clinical diagnosis of herpes progenitalis. CIU, which was inadequately controlled with antihistamines alone, responded dramatically to the addition of acyclovir therapy. Our results may not be applicable to other patients with CIU, especially when there is inadequate evidence of an association with genital herpes. CIU may be associated with recurrent genital herpes simplex infection. In such situations, the addition of acyclovir to therapy may be beneficial., (Copyright 2009 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Two boys and a girl, aged 8, 7 and 4 years old respectively, attended the outpatient clinic suffering from urticaria. The oldest boy was diagnosed with chronic urticaria and angio-oedema, whereas the youngest boy was diagnosed with chronic urticaria only. The little girl had a history of constitutional eczema, and presented with a common cold complicated by acute urticaria. All three patients responded well to treatment with antihistamines. Urticaria is usually not caused by an allergy. The major cause of acute urticaria in childhood is viral infection. Further investigation is not usually necessary. In the majority of cases, chronic urticaria is idiopathic, and maintenance treatment with antihistamines is indicated.

Acute and chronic urticaria may be triggered by infection. Streptococci and Helicobacter pylori are the most frequent acute infectious causes. We present two cases in which we cultured Norovirus in the stool of patients with both acute and chronic urticaria. Noroviruses (genus Norovirus, family Caliciviridae) are a group of single stranded RNA, nonenveloped viruses which cause acute gastroenteritis in humans. Norovirus was recently approved as the official genus name for the group of viruses provisionally described as Norwalk-like viruses (NLV). Therapy is symptomatic. Noroviruses should be regarded as possible infectious trigger for dermatologic diseases. In seeking a focus of viral or bacterial infection for skin diseases with unknown origin, stool cultures should be part of the routine evaluation.

This article describes a transplant recipient with underlying hypocomplementemic urticarial vasculitis syndrome who expressed persistently Epstein-Barr virus nuclear antigen 1 (EBNA1) in peripheral blood. The patient received a bilateral lung transplant and was subsequently followed with monitoring of EBV expression in peripheral blood. Evaluation of viral expression in peripheral blood, serum, and graft tissue was performed with RT-PCR, Q-PCR, indirect immunofluorescence, anti-peptide assays, and in situ hybridization; samples were collected at various time-points up to 91 days post-transplantation. The patient expressed EBNA1 in 8/10 (80%) of the peripheral blood samples tested during the post-transplantation period, and interestingly, even including the day of transplantation. After analyses of indicative EBV mRNA, EBNA1 expression was found mainly to be Qp-initiated EBNA1, known to be important for EBV maintenance. Anti-EBNA1 epitope mapping showed significantly higher and broader antibody responses to EBNA1 epitopes pre-transplantation when compared to normal controls and a matched lung transplant control. Post-transplantation this response was largely diminished but there were still epitopes significantly higher than controls. Our results show the presence of EBV-positive proliferating cells before onset of intensive immunosuppressive treatment. Although no previous connection between EBV and hypocomplementemic urticarial vasculitis syndrome has been reported, it is tempting to speculate that the continuous EBNA1 expression is not caused by immunosuppression or post-transplant lymphoproliferative disease, but may be a factor involved in the etiology of the autoimmune disease.

Background: The etiology of chronic urticaria is undefined, but the potential role of infectious agents as one triggering factor has been suggested. The appearance of chronic urticaria in a 16-year old male after a history of a recent parvovirus B19 (B19) infection led us to investigate the association between B19 and chronic urticaria., Objectives: To investigate whether parvovirus B19 (B19) has a role in chronic urticaria., Study Design: We amplified B19 DNA from skin biopsy samples of 36 adult chronic urticaria patients as well as of 22 healthy controls using two sets of separate primers and probe. Circulating IgG and IgM antibodies to B19 were measured from 27 patients and from all controls., Results: B19 DNA was detected in 18 (50%) skin biopsy samples of 36 patients with chronic urticaria. Unexpectedly, also 14 (64%) skin biopsy samples from 22 healthy controls harbored B19 DNA. All 32 persons with positive B19 PCR findings had circulating IgG-class antibodies to B19 major structural protein VP2, but no IgM antibodies., Conclusion: Our results show that B19 DNA commonly exists in human skin. Therefore, the association between B19 infection and chronic urticaria remains uncertain. However, these findings raise the question whether the skin may constitute a reservoir for B19.

It is well established, that viral infections may trigger urticaria or allergic asthma; however, as viral infections induce T helper 1 polarized responses, which lead to the inhibition of T helper 2 cell development, the opposite would be plausible. We wanted to investigate how viral infections may mediate allergic symptoms in a mouse model; therefore, we infected BALB/C mice with influenza A virus intranasally. Histologic analyses of lung sections and bronchoalveolar lavages were performed. In addition, cells from the mediastinal lymph nodes were restimulated in vitro to analyze which types of cytokines were induced by the flu infection. Furthermore, flu-specific antibody titers were determined and local anaphylaxis was measured after rechallenge with flu antigen. We found that airways inflammation consisted predominately of macrophages and lymphocytes, whereas only a few eosinophils were observed. interferon-gamma but no interleukin-4 and little interleukin-5 could be detected in the culture supernatants from in vitro restimulated T cells from the draining lymph nodes. The antibody response was characterized by high levels of virus-specific IgG2a, IgG2b, and IgG1 and, surprisingly, low levels of virus-specific IgE antibodies. Interestingly, flu-infected mice developed active and passive cutaneous anaphylaxis after rechallenge with flu-antigen. As the passive cutaneous anaphylaxis reaction persisted over 48 h and was significantly lower after passive transfer of the serum, which was IgE depleted, local anaphylaxis seemed to be mediated predominately by specific IgE antibodies. Taken together, our results demonstrate that mice infected with flu virus develop virus-specific mast cell degranulation in the skin. Our results may also have implications for the pathogenesis of urticaria or other atopic disorders in humans.

Objective: To study the prevalence of hepatitis C virus (HCV) and hepatitis G virus (HGV) infection in patients with chronic urticaria., Design: Prospective case-control study and literature review., Setting: Dermatology department of an academic medical center in Strasbourg, France., Patients: One hundred ten consecutive patients with typical urticaria lasting longer than 2 months were seen between March 1, 1997, and August 31, 1998. None had a history of viral hepatitis. Age- and sex-matched patients (n = 110) seen in the same department and during the same period were included for controls. None of the controls had a history of urticaria, pruritic dermatosis, or hepatitis., Main Outcome Measures: The detection of HCV antibodies through a third-generation enzyme-linked immunosorbent assay. To detect early HCV infection without plasmatic antibodies, genomic amplification of HCV RNA was carried out in all patients using 2 different methods. Hepatitis G virus RNA was detected only by genomic amplification. All measures were planned before data collection., Results: Antibodies to HCV were found in 1 patient with urticaria and in 1 of the control group (0.9% of each group). None had circulating HCV RNA, and liver function test results were within the reference range. Genomic amplification without HCV antibodies was not observed. Two patients with urticaria and 2 of the control group (1.8% of each group) had circulating HGV RNA, but they had neither coinfection with HCV nor changes in their liver function test results., Conclusions: Systematic HCV screening in patients with chronic urticaria is not cost-effective, at least in Europe, because hepatitis C rates were similar to those of the general population. We could not confirm the hypothesis that urticaria occurs in an early phase of HCV infection-ie, before evidence of HCV can be detected by serologic testing. Hepatitis C virus is unlikely to be the cause of urticaria in the infected patient detected in this study because of the absence of HCV RNA and changes on liver function tests. Hepatitis G virus is also unlikely to be a cause of urticaria, as the rate of HGV positivity in this study was even lower than that in the general French population.