A case for palliative dermatology: COVID-19-related dermatoses.

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.

Covid-19 pandemic and the skin.

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.

Serological evidence that activation of ubiquitous human herpesvirus-6 (HHV-6) plays a role in chronic idiopathic/spontaneous urticaria (CIU).

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.

Herpesvirus-associated acute urticaria: an age matched case-control study.

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.

Screening of hepatitis C virus genotypes in urticaria patients in Saudi Arabia.

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.

Autoimmune disease: A role for new anti-viral therapies?

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.

EBNA1 expression in a lung transplant recipient with hypocomplementemic urticarial vasculitis syndrome.

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.

Presence of parvovirus B19 DNA in chronic urticaric and healthy human skin.

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.

Infection with influenza a virus leads to flu antigen-induced cutaneous anaphylaxis in mice.

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.

The rash of measles is caused by a viral infection in the cells of the skin: a case report.

Measles skin rash was immunohistochemically examined in an effort to detect virus antigen in skin samples taken from a 15-year-old girl with measles. A sectioned specimen obtained by punch biopsy from a 2nd-day skin lesion showed localized parakeratosis and acanthosis with multinucleated giant cells in the epidermis, thickening and cellular edema of epithelia in the hair follicles, and vascular dilation in the papillary plexus. Measles virus antigen was detected by ABC immunoperoxidase in the epidermis, follicular epithelia, and lympho-histiocytic cell infiltrates in the upper of the dermis. This rash deemed to be caused in part by direct viral infection of the epidermal cells.