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Background: Limited information exists on mucocutaneous disease and its relation to course of COVID-19., Objective: To estimate prevalence of mucocutaneous findings, characterize morphologic patterns, and describe relationship to course in hospitalized adults with COVID-19., Methods: Prospective cohort study at 2 tertiary hospitals (Northwell Health) between May 11, 2020 and June 15, 2020., Results: Among 296 hospitalized adults with COVID-19, 35 (11.8%) had at least 1 disease-related eruption. Patterns included ulcer (13/35, 37.1%), purpura (9/35, 25.7%), necrosis (5/35, 14.3%), nonspecific erythema (4/35, 11.4%), morbilliform eruption (4/35, 11.4%), pernio-like lesions (4/35, 11.4%), and vesicles (1/35, 2.9%). Patterns also showed anatomic site specificity. A greater proportion of patients with mucocutaneous findings used mechanical ventilation (61% vs 30%), used vasopressors (77% vs 33%), initiated dialysis (31% vs 9%), had thrombosis (17% vs 11%), and had in-hospital mortality (34% vs 12%) compared with those without mucocutaneous findings. Patients with mucocutaneous disease were more likely to use mechanical ventilation (adjusted prevalence ratio, 1.98; 95% confidence interval, 1.37-2.86); P < .001). Differences for other outcomes were attenuated after covariate adjustment and did not reach statistical significance., Limitations: Skin biopsies were not performed., Conclusions: Distinct mucocutaneous patterns were identified in hospitalized adults with COVID-19. Mucocutaneous disease may be linked to more severe clinical course., Competing Interests: Conflicts of Interest Dr Garg has received honoraria from AbbVie, Amgen, Boehringer Ingelheim, Incyte, Janssen, Novartis, Pfizer, UCB, and Viela Bio. The rest of the authors have no conflicts to disclose., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Abstract: Biopsies were taken from 4 patients who presented to their dermatologist with violaceous papules and plaques of the dorsal toes (COVID Toes) associated with varying degrees of severe acute respiratory syndrome coronavirus 2 exposure and COVID-19 testing. Major histopathologic findings were lymphocytic eccrine inflammation and a spectrum of vasculopathic findings to include superficial and deep angiocentric-perivascular lymphocytic inflammation, lymphocytes in vessel walls (lymphocytic vasculitis), endothelial swelling, red blood cell extravasation, and focal deposits of fibrin in both vessel lumina, and vessel walls. Interface changes were observed to include vacuolopathy and apoptotic keratinocytes at the basement membrane. Immunostains showed a dominant T-cell lineage (positive for T-cell receptor beta, CD2, CD3, CD5, and CD7). B-cells were rare and clusters of CD123-positive dermal plasmacytoid dendritic cells were observed surrounding eccrine clusters and some perivascular zones. The consistent perieccrine and vasculopathic features represent important pathologic findings in the diagnosis of COVID toes and are suggestive of pathogenetic mechanisms. Clinicopathologic correlation, the epidemiological backdrop, and the current worldwide COVID-19 pandemic favor a viral causation and should alert the physician to initiate a workup and the appropriate use of COVID-19 testing., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

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.)

Context: Various skin manifestations have been reported in coronavirus disease. It may be difficult to determine the etiology of these lesions in view of the increased frequency of handwashing during the pandemic, along with occurrences of irritant contact dermatitis and allergic contact dermatitis due to disinfectant use; usage of herbal medicine and supplements to strengthen the immune system; and urticarial or maculopapular drug eruptions due to COVID-19 treatment. The variety of associated skin manifestations seen with COVID-19 makes it challenging to identify virus-specific skin manifestations. Petechiae, purpura, acrocyanosis and necrotic and non-necrotic purpura, which can be considered as manifestations of vascular involvement on the skin, have been reported., Case Report: Here, we report a case of eruptive cherry angiomas, which was thought to have developed due to COVID-19, with a papulovesicular rash on distal extremities that progressed over time to reticular purpura., Conclusion: The case presented had a papulovesicular rash at the onset, which evolved to retiform purpura, and eruptive cherry angiomas were observed. It should be kept in mind that dermatological signs may vary in patients with COVID-19.

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: There are two distinctive acral manifestations of COVID-19 embodying disparate clinical phenotypes. One is perniosis occurring in mildly symptomatic patients, typically children and young adults; the second is the thrombotic retiform purpura of critically ill adults with COVID-19., Objectives: To compare the clinical and pathological profiles of these two different cutaneous manifestations of COVID-19., Methods: We compared the light microscopic, phenotypic, cytokine and SARS-CoV-2 protein and RNA profiles of COVID-19-associated perniosis with that of thrombotic retiform purpura in critical patients with COVID-19., Results: Biopsies of COVID-19-associated perniosis exhibited vasocentric and eccrinotropic T-cell- and monocyte-derived CD11c + , CD14 + and CD123 + dendritic cell infiltrates. Both COVID-associated and idiopathic perniosis showed striking expression of the type I interferon-inducible myxovirus resistance protein A (MXA), an established marker for type I interferon signalling in tissue. SARS-CoV-2 RNA, interleukin-6 and caspase 3 were minimally expressed and confined to mononuclear inflammatory cells. The biopsies from livedo/retiform purpura showed pauci-inflammatory vascular thrombosis without any MXA decoration. Blood vessels exhibited extensive complement deposition with endothelial cell localization of SARS-CoV-2 protein, interleukin-6 and caspase 3; SARS-CoV-2 RNA was not seen., Conclusions: COVID-19-associated perniosis represents a virally triggered exaggerated immune reaction with significant type I interferon signaling. This is important to SARS-CoV-2 eradication and has implications in regards to a more generalized highly inflammatory response. We hypothesize that in the thrombotic retiform purpura of critically ill patients with COVID-19, the vascular thrombosis in the skin and other organ systems is associated with a minimal interferon response. This allows excessive viral replication with release of viral proteins that localize to extrapulmonary endothelium and trigger extensive complement activation., (© 2020 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

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 growing number of skin lesions during the COVID-19 pandemic are being recognized. Acral ischemic lesions identical to chilblains are most typical in children and young adults. We report an infant girl, aged 1 month and 29 days, with a peculiar reticulated purpuric eruption on her soles, with positive immunohistochemistry for SARS-CoV-2 in the endothelia of dermal blood vessels. The patient had an excellent outcome without specific therapy., (© 2020 Wiley Periodicals LLC.)

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.)

Acute respiratory failure and a systemic coagulopathy are critical aspects of the morbidity and mortality characterizing infection with severe acute respiratory distress syndrome-associated coronavirus-2, the etiologic agent of Coronavirus disease 2019 (COVID-19). We examined skin and lung tissues from 5 patients with severe COVID-19 characterized by respiratory failure (n= 5) and purpuric skin rash (n = 3). COVID-19 pneumonitis was predominantly a pauci-inflammatory septal capillary injury with significant septal capillary mural and luminal fibrin deposition and permeation of the interalveolar septa by neutrophils. No viral cytopathic changes were observed and the diffuse alveolar damage (DAD) with hyaline membranes, inflammation, and type II pneumocyte hyperplasia, hallmarks of classic acute respiratory distress syndrome, were not prominent. These pulmonary findings were accompanied by significant deposits of terminal complement components C5b-9 (membrane attack complex), C4d, and mannose binding lectin (MBL)-associated serine protease (MASP)2, in the microvasculature, consistent with sustained, systemic activation of the complement pathways. The purpuric skin lesions similarly showed a pauci-inflammatory thrombogenic vasculopathy, with deposition of C5b-9 and C4d in both grossly involved and normally-appearing skin. In addition, there was co-localization of COVID-19 spike glycoproteins with C4d and C5b-9 in the interalveolar septa and the cutaneous microvasculature of 2 cases examined. In conclusion, at least a subset of sustained, severe COVID-19 may define a type of catastrophic microvascular injury syndrome mediated by activation of complement pathways and an associated procoagulant state. It provides a foundation for further exploration of the pathophysiologic importance of complement in COVID-19, and could suggest targets for specific intervention., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In Taiwan, a petechial haemorrhage disease associated with mortality has affected marbled eels (Anguilla marmorata). The eels were revealed to be infected with adomavirus (MEAdoV, previously recognized as a polyoma-like virus). In this study, cell line DMEPF-5 was established from the pectoral fin of a diseased eel. DMEPF-5 was passaged >70 times and thoroughly proliferated in L-15 medium containing 2%-15% foetal bovine serum at 20-30°C. Transcripts of neural cell adhesion molecule 1 and nestin genes, and nucleic acids of MEAdoV and a novel reovirus (MERV) in the cells were demonstrated by reverse transcription-polymerase chain reaction analysis. Phylogenetic analysis revealed that the AdoV LO8 proteins mostly relate to adenovirus adenain, whereas MERV is close to American grass carp reovirus in Aquareovirus G, based on a partial VP2 nucleotide sequence. DMEPF-5 cells are susceptible to additional viral infection. Taken together, the marbled eels with the haemorrhagic disease have coinfection with MEAdoV and MERV, and the pathogenic role of MEAdoV and MERV warrants research. DMEPF-5 has gene expression associated with mesenchymal stem and progenitor cells and is the first cell line persistently infected with adomavirus and aquareovirus. DMEPF-5 can facilitate studies of such viruses and haemorrhagic disease., (© 2019 John Wiley & Sons Ltd.)

Importance: The Zika virus epidemic has been declared a public health emergency of international concern by the World Health Organization. We describe the mucocutaneous features and histologic correlation in a patient with the acute Zika virus infection., Observations: We observed the presence of a diffuse papular descending eruption, petechiae on the palate, and hyperemic sclerae in a 44-year-old man returning from Puerto Rico with confirmatory testing for the Zika virus., Conclusions and Relevance: A detailed awareness of mucocutaneous findings associated with Zika virus infection will support its early recognition and will facilitate elimination of Zika infection from consideration for concerned patients who present with other, more common erythematous eruptions.

Introduction: The association of fever and petechiae in children is one of the most alarming findings for a paediatrician. To quickly distinguish between benign and life-threatening conditions is challenging in many cases. We aimed to evaluate the clinical practice of children presenting with fever and petechiae as initial symptoms., Methods: 41 patients (age 3 months-11 years) presenting with fever and petechiae were identified in an Emergency Paediatric Assessment Unit over a period of 9 months. General data, symptoms and signs were assessed for each patient. The work-up consisted in: complete blood count, inflammatory tests, coagulation tests, Monospot test, nasopharyngeal rapid tests, blood culture, and cerebrospinal fluid culture where appropriate., Results: Most children were <5 years of age (70.7%). Female to male ratio was 1:2.4. The most common clinical diagnoses were: viral respiratory illness (48.8%, 20/41) and upper respiratory tract infection (17.1%, 7/41). Meningococcal disease was found in one case. CRP>6 mg/l was poorly correlated with serious illness. The following variables were strongly associated with serious illness: ill appearance, shivering, lethargy, back rigidity, ESR>50 mm/h and prolonged capillary refill time. 59% (24/41) of children were treated with antibiotics, however, at discharge 42%(10/24) of them, did not have a work-up suggestive for a bacterial illness., Conclusions: Screening for low prevalence but high morbidity conditions, as the meningococcal disease, with an extensive work-up is time and resource consuming and may lead to unmotivated antibiotic use. Larger studies are needed to change the emergency practice for management of fever and rash.

Human Parvovirus B19 (B19V) infection usually causes erythema infectiosum (EI). In recent decades, several uncommon exanthems have been described in association with B19V. Recently, haemorrhagic manifestations such as purpuric-petechial rash have been reported. We describe an unusual paediatric case of B19V associated with generalized petechial eruption, and a review of the recent literature.

Human immunodeficiency virus (HIV) infection is growing medical concern worldwide. There are many types of glomerulonephritis which are associated with HIV infection. We report a case of a 53-year-old Korean man with an HIV infection, who was developed nephritic range proteinuria and purpura with elevated IgA level rasing a possibility of Henoch-Schölein Purpura (H-S purpura). However, renal biopsy showed "lupus-like feature" glomerulonephritis without clinical or serologic evidence of systemic lupus erythematosus. Although baseline renal function was maintained without further need for maintenance dialysis following anti-retroviral therapy (ART) and steroid, patient died from uncontrolled gastrointestinal bleeding.

Background: Parvovirus B19 can cause petechial rashes in the acute phase of illness as well as erythema infectiosum (fifth disease) during convalescence. This petechial rash is often called "gloves and socks" syndrome because of the typical distribution of the eruption. However, involvement of other sites (e.g., intertriginous area) and generalized involvement have been recently recognized. We report here a patient with parvovirus-associated petechiae and cephalhematoma., Case Presentation: The patient was a previously healthy 10-year-old boy. There was a family history of fatal bleeding; his sister died of intracranial bleeding with an uncertain cause at the age of 5 months. The patient was admitted to our hospital because of sudden onset of cephalhematoma associated with fever. He reported that he had no recent head trauma but that he massaged his scalp on the day before admission. On admission, his temperature was 38.8°C; otherwise, he was in a stable condition. Besides cephalhematoma, petechial rashes were present on his trunk and limbs. The initial laboratory tests were essentially normal, including platelet count and coagulation tests. Expanded laboratory tests were repeated to explore the etiology of his skin hemorrhage, all of which indicated that hematological disorders were unlikely. His symptoms subsided spontaneously over the next few days and he was discharged uneventfully. Anti-parvovirus IgM titer was elevated during hospitalization and typical erythema infectiosum was seen approximately 1 week after discharge. During 6 months follow-up, he remained stable without recurrence of a hemorrhagic episode. Finally, we concluded that his cephalhematoma was responsible for acute parvoviral infection., Conclusions: This is believed to be the first report describing a possible association between parvovirus B19 infection and cephalhematoma. Parvovirus B19 infection should be considered in the differential diagnosis of children who present with unexplained hemorrhage such as cephalhematoma or petechiae.

Background: Children with petechial rash are more likely to undergo invasive diagnostics, to be treated with antibiotics for potential bacterial infection and to be hospitalized. However, viruses have also been associated with petechial rash. Nonetheless, a systematic analysis of viral infections with modern available techniques as quantitative real-time polymerase chain reaction in the context of petechial rash is lacking. The purpose of this pediatric study was to prospectively uncover viral pathogens that may promote the emergence of petechiae and to analyze the correlation with the clinical characteristics and course., Methods: We conducted a prospective study in children (0 to 18 years) presenting with petechiae and signs or symptoms of infection at the emergency department between November 2009 and March 2012. In nasopharyngeal aspirates the following viruses were analyzed by quantitative real-time polymerase chain reaction: cytomegalovirus, Epstein-Barr virus, parvovirus B19, influenza A and B, parainfluenza viruses, human respiratory syncytial virus A and B, human metapneumovirus, rhinovirus, enterovirus, adenovirus, human coronavirus OC43, 229E, NL63 and human bocavirus., Results: A viral pathogen was identified in 67% of the analyzed 58 cases with petechial rash. Virus positive patients showed a significantly higher incidence of lower respiratory tract infections. Forty-one percent were viral coinfections, which were significantly younger than virus negative patients, had a higher leukocyte count and were hospitalized for a longer time., Conclusions: A petechial rash is frequently associated viral single- and coinfections and can rapidly be identified via quantitative real-time polymerase chain reaction.

Papular-purpuric gloves and socks syndrome is a rare, highly contagious dermatosis caused by parvovirus B19, which may result in the abrupt cessation of red blood cell production in patients with preexisting hematological diseases. It affects predominantly children and young adults and has an unusual presentation.

Papular-purpuric "gloves and socks" syndrome is a distinctive dermatosis featuring acral pruritus, edema, and petechiae. It has been attributed in most--but not all--reported cases to Parvovirus B19 infection, on the grounds of serological proof of recent infection or detection of viral DNA by polymerase chain reaction in patient serum or biopsies. We report the immunohistochemical detection of Parvovirus B19 VP2 structural protein in the endothelial lining of dermal blood vessels in 3 examples of Papular-purpuric "gloves and socks" syndrome and review previously described immunohistochemical investigations in cutaneous involvement by this infection.

Background: Papular-purpuric gloves-and-socks syndrome, characterized by focal acral purpuric eruptions with a symmetrical distribution, is a rare but representative purpuric dermatosis closely associated with parvovirus B19 (PVB19) infection. However, several atypical presentations such as involvement of other sites and generalized involvement have been recently reported in PVB19 infected patients. Such multifaceted features can cause considerable confusion when making a diagnosis of purpuric eruption associated with PVB19., Objectives: Describe two febrile patients with atypical presentation of papular-purpuric eruptions due to PVB19 infection and discuss the distinctive features of purpuric-petechial eruptions associated with PVB19 infection., Study Design: Case reports and viral diagnosis by serologic tests and real-time PCR for PVB19 DNA in the serum., Results: One presented with "asymmetrical gloves without socks" distribution of papular purpuric eruptions accompanied by asymmetrical intertriginous involvement, the other with generalized distribution characterized by prominent intertriginous and truncal involvement. Both cases were followed by erythema infectiosum. Paired serum antibody analysis and real-time PCR indicated the link between the development of papular purpuric eruption and the viremic phase of primary PVB19 infection., Conclusions: PVB19 infection should be considered in any patient presenting with a petechial or purpuric eruption of unclear origin, and not solely for PPGSS type presentations. Therefore, we propose a simple name "PVB19-associated purpuric-petechial eruption" to describe polymorphous purpuric-petechial eruptions due to PVB19 infection, coinciding with the viremic phase of primary infection and infectivity, characterized by a self-limiting course with a benign prognosis and common histological findings., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Chikungunya (CHIK) is an emerging viral disease with a myriad of cutaneous manifestations., Aims: The aim of our study was to document the morphology and evolution of skin lesions in cases presenting with fever, purpuric macules and vesiculobullous lesions, to confirm its causative relationship with CHIK, and to investigate further in order to delineate possible mechanisms of bulla formation in these cases., Materials and Methods: A prospective, descriptive hospital-based study was carried out at a tertiary health care centre in Kerala. A total of 10 patients were enrolled in the study and investigated., Results: All cases had morbilliform eruption prior to onset of purpuric macules. Eight cases developed vesiculobullous lesions that arose either de novo or over a part or whole of the purpuric macules. Skin lesions resolved within an average of 7.6 days leaving post-inflammatory hypopigmentation. IgM CHIK enzyme-linked immunosorbent assay (ELISA) was positive in all 10 patients. Tzanck smear from the bullae showed lymphocytes in most cases along with acantholytic cells, necrotic keratinocytes or occasional neutrophils. Skin biopsy showed intraepidermal or subepidermal bullae. Immunohistochemistry revealed predominantly CD8 positive T lymphocytes in the infiltrate. The prognosis was good with supportive management alone., Discussion: The clinical features in our cases are comparable to the 3 previous reports of vesiculobullous lesions in CHIK affected infants. Based on the current evidence, we hypothesize that at least 2 mechanisms are at play for these skin lesions; CHIK virus induced keratinocyte necrosis followed by a cytotoxic immune response, and possible modulation of rash by drugs., Conclusion: With severe epidemics of CHIK spreading from Asia and Africa to the Western hemisphere, we must consider bullous CHIK as a differential diagnosis in cases with fever and purpuric and vesiculobullous lesions., (© 2011 The International Society of Dermatology.)

We describe the case of a 12-year-old boy with gloves and socks syndrome caused by coinfection with HHV-6 and PVB19, and review the published cases from 5 to 18 years of age to profile the disease in this age group. The review of the literature yielded 25 cases of gloves and socks syndrome. Most patients were febrile and had acute PVB19 infection.

The authors describe a Thai newborn boy who was presented with petechiae, hepatosplenomegaly and pancytopenia at birth caused by congenital HIV infection. His clinical presentations were appeared on the early onset after birth. The bone marrow finding has shown hypocellularity which was also rare in HIV-infected children.

Although asymptomatic joint involvement and arthralgias are frequent in patients with hepatitis C virus chronic infection (HCV), a true arthritis affects only up to 4% of the subjects. HCV-related arthritis (HCVrA) is usually distinguished in two clinical subsets: a more frequent symmetrical polyarthritis (SP), similar to rheumatoid arthritis but much less serious, and an intermittent mono-oligoarthritis (IMO) that involves medium and large sized joints, mainly the ankle. This latter subset is strictly related to the presence of HCV-induced mixed cryoglobulinemia and its cutaneous manifestations, in particular purpura. According to recent reports, anti-CCP antibodies are considered very useful in differentiating the SP subset from rheumatoid arthritis. The treatment of HCVrA is still largely empirical because few studies have analyzed this topic. However, COXIBs, NSAIDs, low doses of corticosteroids, hydroxychloroquine and less frequently methotrexate and penicillamine have been used with partial or complete control of symptoms. On the basis of recent studies, the administration of cyclosporine also seems to be sufficiently safe. The scarcely aggressive nature of HCVrA does not favour the use of anti-TNF agents. Specific anti-viral therapy (interferon-alpha+ribavirin) must be accurately evaluated because interferon-alpha can induce the development or the worsening of several autoimmune HCV-related disorders including arthritis.

Zebrafish is a model animal for studies of genetics, development, toxicology, oncology, and immunology. In this study, infectious spleen and kidney necrosis virus (ISKNV) was used to establish an infection in zebrafish, and the experimental conditions were established and characterized. Mortality of adult zebrafish infected with ISKNV by intraperitoneal (i.p.) injection exceeded 60%. ISKNV can be passed stably in zebrafish for over ten passages. The ailing zebrafish displayed petechial hemorrhaging and scale protrusion. Histological analysis of moribund fish revealed necrosis of tissue and enlarged cells in kidney and spleen. The real-time RT-PCR analysis of mRNA level confirmed that ISKNV was replicated in zebrafish. Immunohistochemistry and immunofluorescence analyses further confirmed the presence of ISKNV-infected cells in almost all organs of the infected fish. Electron microscope analyses showed that the ISKNV particle was present in the infected tissues. The establishment of zebrafish infection model of ISKNV can offer a valuable tool for studying the interactions between ISKNV and its host.

Two atypical cases of parvovirus B19 infection occurred consecutively within a family. A 14 year-old patient presented an extended papular-purpuric "gloves and socks" syndrome and two weeks later his mother developed a predominantly unilateral purpuric rash in the limbs with severe malaise. Specific IgM antibodies in the boy and polymerase chain reaction (PCR) and serology in the mother, confirmed parvovirus B19 infection. We emphasize the variable presentation of B19 infection within a family. The importance of etiologic studies in the presence of atypical exanthemas and the utility of PCR in the diagnosis of B19 are underscored.

The papular purpuric gloves and socks syndrome (PPGSS) is an uncommon dermatosis with a typical purpuric exanthem limited to hands and feet; it occurs mainly in young adults. We report a case of a 19-year-old man with an acute febrile illness accompanied by purpuric and papular lesions located mostly on the dorsal areas of his hands and feet. Serologic analysis for parvovirus B19 yielded positive results. The diagnosis of PPGSS was made. The eruption cleared without therapy in 12 days with plantar and palmar desquamation. Parvovirus B19 and some other viral infections have been proven to be causative agents of this syndrome.